Laser apparatus and method for refractive surgery

ABSTRACT

An ultrashort pulsed laser instrument is used to perform refractive surgery. The invention operates in ablative and incisional modalities. In the ablative mode, spiral ablation disks ( 10 ) consisting of individual laser pulses ( 40 ) are produced at high scanning speeds. Ablation profile ( 11 ) may be produced in cornea ( 22 ) by stacking and arranging multiple ablation disks ( 10 ) to produce a specified shape change. Placement of ablation disks ( 10 ) is assisted by an optical tracking and control system that compensates for eye motion. A preferred embodiment allows for ablative corrections to be performed on non-planar posterior surface ( 112 ) of a laser cut flap affixed to registration platen ( 120 ), thereby avoiding exposing the eye interior to high radiant power. Laser cut and contrast agent dyed fiduciary marks ( 30 ) may serve as reference features for the optical tracking system. Incisional procedures, such as corneal flaps for LASIK, may also be performed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. NonprovisionalUtility application Ser. No. 13/244,446 filed Sep. 24, 2011, entitled“LASER APPARATUS AND METHOD FOR REFRACTIVE SURGERY,” which applicationclaims benefit of U.S. Provisional Utility Application No. 61/386,507filed Sep. 25, 2010, the entire disclosures of which are incorporated byreference herein.

FEDERALLY SPONSORED RESEARCH

Not Applicable

SEQUENCE LISTING OR PROGRAM

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of Invention

This invention relates to the area of human vision correction,specifically relating to the use of short pulse laser beams to preciselyremove ocular tissue to change the refractive power of the human eye.

2. Background of the Invention

The invention relates to procedures and apparatus for performingrefractive surgery in the central aspect of the cornea to correctrefractive errors of the eye. The invention uses ultrashort pulsed laserto perform all aspects of the corneal surgery, including the creation ofincisions and the direct ablation of corneal tissue. In particular, theinvention replaces the use of UV ablating lasers in procedures such aslaser-assisted in-situ keratomileusis (LASIK) with an ultrashort pulsedlaser.

Corneal Refractive Laser Surgery

Modern corneal refractive surgery techniques draw upon the original workof Dr. Jose I. Barraquer. Briefly, in 1958, Dr. Barraquer firstdeveloped keratomileusis techniques based on the removal of a lenticularvolume of corneal tissue by mechanical means. In 1990, Pallikaris et alreported the use of an excimer laser was used to ablate the lenticularvolume in the first LASIK cases. The development of LASIK and relatedprocedures is described in Section Three, pages 147-222 of the text book“Refractive Surgery”, 2nd edition, 2007, edited by Dimitri Azar.

In the development of corneal refractive correction with lasers, directablation of the corneal anterior surface with an ultraviolet (UV) laserwas used. An early example is the method of L'Esperance, Jr. in U.S.Pat. No. 4,665,913. The UV laser was typically an excimer laser. Thelaser ablation was performed with repeated patterns of laser pulsesarranged in a specific geometry. The pattern of ablating pulses produceda change in the corneal shape and therefore the refractive power of theeye. This procedure is called photorefractive keratectomy (PRK). Thelimits of this approach include the fact that direct ablation of theanterior layers of the cornea, including Bowman's layer and the anteriorcorneal stroma, produce tissue remodeling and a wound healing responsethat limit and degrade the optical outcome.

Laser-assisted in situ keratomileusis (LASIK) was developed to overcomethe limits of PRK. In U.S. Pat. No. 4,840,175, Peyman first detailed themethod which later came to be known as LASIK. In LASIK, a mechanicalblade first makes a corneal flap cut. Subsequent manual lifting of theflap exposes the inner corneal tissue, referred to as the cornealstroma. The stroma is then subjected to an ablating UV laser beam. Theablating UV laser beam removes a volume of corneal tissue according to aspecific mathematical prescription for producing the desired curvaturechange. In a later development, Munnerlyn in U.S. Pat. No. 5,163,934,employed a difference of sphere formulation to determine the lenticularvolume to be removed for a treatment of myopia. The success of LASIK wasswift, but used a two-stage, two-instrument procedure. A significantlimitation of LASIK is the reliability, precision and quality of theblade cuts to produce the corneal flap. A second limitation is therequirement that nomograms be developed to compensate for the biologicalresponse to ablation, and to the geometry-dependent efficiency of UVlaser ablation of the corneal stroma. A third limitation is that the lowspatial frequency of the ablation patterns realizable with excimer laserablation. That is, the lateral size of the ablation compared to theablation depth of a single pulse makes it difficult to stack pulses in away that allows for arbitrary ablation profiles. Typically, the profilesin LASIK and PRK vary slowly, which from a visual outcomes point of viewis rather good. However, if a small amount of tissue is to be removed,such as may occur in a complication of refractive surgery, or if ahigher order aberration is to be corrected by removal of a volume oftissue having relatively steeply angled features, large spot excimerablation may not be efficacious.

LASIK and PRK are performed using a UV laser, typically an excimerlaser, to perform the ablative part of the procedure. Examples ofexcimer laser keratomes include the Visx Star S4 from Abbott MedicalOptics, Santa Ana, Calif.; the Technolas 217A from Technolas PerfectVision GmbH, Munich, Germany; or the LADARVision 4000 and the AllegrettoWave from Alcon Laboratories, Inc., Fort Worth, Tex.

An alternative to LASIK and PRK was suggested and developed by Bille andJuhasz in U.S. Pat. No. 4,907,586 and further refined in U.S. Pat. No.5,993,438. In this method, a focused ultrashort pulsed laser beam isscanned inside the cornea to create a defined volume of vaporized tissueconsisting of many individual small-scale photodisruptions. The volumeof tissue would be vaporized and ultimately resorbed by the surroundingcorneal tissue. The resulting new corneal shape would produce thedesired refractive correction. This approach is referred to asintrastromal or intrastromal ablation. A picosecond laser instrument byIntelligent Surgical Lasers was developed for this procedure.Limitations to the method were several. One limitation is the relativelylarge volumes of vapor produced in the stroma which limit the amount oftissue that can be destroyed or removed. A second limitation is that thevaporization of tissue for the purpose of altering the shape of thecornea through relaxation of the overlying anterior surface is limitedby the natural stiffness of the corneal membranes. The native stiffnessof the corneal limits the size of the refractive change that can beproduced in this method.

Ultrashort pulsed lasers were commercially introduced into cornealrefractive surgery with the development of femtosecond laser flap cutterinstruments. Mourou et al in U.S. Pat. No. 5,656,186 described a methodfor using femtosecond pulses which allows for a more deterministic andprecise machining of materials, including biological tissues, relativeto picosecond lasers. Femtosecond lasers assist in the LASIK procedureby replacing the mechanical microkeratomes used in the corneal flapcutting step. The corneal cuts produced are precise and can havearbitrary three dimensional shapes, surpassing what can be achieved withmechanical blades. A limitation of the approach is that the actualrefractive correction still requires the use of a second laser, namelyan excimer laser.

Incisional ultrashort pulsed laser keratomes generate, process anddeliver a train of scanned, tightly focused ultrashort laser pulses ontoor into the volume of a fixed or immobilized cornea. The laser sourcesused generally employ a chirped pulse amplification technique with alarge bandwidth lasing medium, such as Ti:S, Nd:glass or Yb:fiber.Typically, the laser pulses energies range from 0.1-10 microJoules, thepulse widths are <1 picosecond, the beam quality isnear-diffraction-limited, and the wavelength falls between the NIR andthe visible (typ 800-1100 nm) so as to avoid significant heating ofwater or tissue by linear absorption in the corneal tissue. Commerciallyavailable instruments operate at laser repetitions between 30 kHz and 2MHz, depending on the design, model and manufacturer. A high speed 2Dbeam scanner in combination with a high numerical aperture focusingobjective allows for the precise placement of tightly focused spotsthroughout the volume of the human cornea. In a typical femtosecondlaser keratome the cornea is fixed with respect to the keratome opticalaxis and the cornea is lightly held in place and applanated by a contactglass and suction ring.

A purely incisional approach to refractive surgery using a singleultrashort pulsed laser instrument was taught by Juhasz in U.S. Pat. No.6,110,166. In this approach, multiple laser cuts define a disk-shapedblock of corneal stromal tissue underlying a laser-cut flap. The flap ismanually lifted and the disk-shaped corneal plug or disk is manuallyremoved. When the flap is replaced, the change in the corneal shaperesulting from the missing corneal tissue lenticle produces anappropriate change in refractive power. This change can be accomplishedwithout the need for an ablation step by a UV laser. The approach wassimilar to an earlier refractive surgery performed with a mechanicalblade. The mechanical approach was called automated lamellarkeratoplasty or ALK, introduced by Ruiz et al in U.S. Pat. No.5,133,726. A limitation of both the ALK and the femtosecond laserkeratomileusis procedure was the relatively poor refractive outcomesassociated with removing a disk of planar geometry, rather than a diskof the ideal lenticule shape according to Munnerlyn and others.

An improved approach over Juhasz is found in United States PatentApplication No. 20080319428 of Weichmann et al. The volume of thestromal disk of tissue to be laser cut and manually removed haveanterior and posterior surfaces having curvatures rather than beingplanar. The invention advantageously allows for the realization of idealshapes of the tissue to be removed. A limitation is that the tissue tobe removed manual after cutting may tear or fragment, and cannot easilybe removed by laser or by other means. A related limitation is that theaxial thickness of the tissue to be removed may be associated with aminimum thickness. Some refractive corrections may require cutting athin cross section volume of tissue. If the tissue is too thin, it maybe too friable. This aspect places limitations on the ranges ofpotential refractive corrections achievable by this method. A furtherlimitation is that the gas produced in the first portion of tissuevaporized may produce movement or changes in the cornea that interferewith the vaporization of subsequent portion of tissue.

U.S. Pat. No. 4,907,586 also contains a method of corneal refractivesurgery in which the optical properties of the cornea are directlyaltered by a scanning ultrashort pulsed laser. In this method, index ofrefractive of the targeted volume produces the desired refractivecorrection. A limitation of this method is the size and stability of therefractive changes to the cornea.

Direct Ablation of Tissue

In LASIK, excimer lasers directly photoablate the corneal tissue theyimpinge upon. The controlled ablation of corneal stroma tissue producesthe desired shape change.

Ultrashort pulsed lasers, such as femtosecond lasers, are widely used toincise cornea through the mechanism of photodisruption. Present clinicaluse of ultrashort pulsed lasers in the eye employs photodisruption andnot the true ablation associated with excimer lasers in cornea. That is,ultrashort pulsed lasers are used to cut cornea rather than ablate it.This is quite sensible in that the natural advantage of using anultrashort pulsed laser in transparent tissue is that highly localized,small photodisruption events can be arranged to create cut planes orsurfaces.

Some confusion exists in the art about the term “ablation”. Whenultrashort pulsed lasers are used in ophthalmic surgery, thelaser-tissue interaction is generally the creation of incisions throughthe cumulative effect of many individual photodisruption events. Inphysical processes, ablation refers to the physical processes, such asmelting and vaporizing, that result in the ejection of material from theablation site. The confusion is likely due to the use of the termablation in medicine. In medical usage, ablation means the localizeddestruction of tissue, but not usually the physical ejection of tissuethrough melting or vaporization.

An aspect of my invention is physical ablation of corneal and oculartissue with ultrashort pulsed lasers. I therefore differentiate betweenthe usage of the term “ablation” in the prior art of ultrashort pulselasers and the meaning of term is used in my invention. Here, when I usethe term “ablation” with ultrashort pulsed lasers, I mean the physicalremoval of tissue resulting from the laser interaction, whether as aresult of a photodisruption event or by some other interaction.Typically I use the term “ablative mode” in this context. When referringto the creation of cuts or incisions, I will use the term “incisionalmode”.

Two examples of this confusion in terminology are found in Zhang et al(“Morphologic and histopathologic changes in the rabbit cornea producedby femtosecond laser-assisted multilayer intrastromal ablation”, IOVS,May 2009, Vol. 50, No. 5.) and Wang et al (“In-vivo intratissue ablationby nanojoule near-infrared femtosecond laser pulses”, Cell Tissue Res2007, Vol. 328:515-520) In the first reference, the authors use the termablation, but the actual laser-tissue interaction in the cornea wasintrastromal photodisruption, which was arranged to create multipledissection planes inside the cornea. In the second reference, theauthors also use the term ablation, but again the laser-tissueinteraction was the photodisruptive destruction of corneal tissue on asmall scale by nanoJoule laser pulses. True ablation was not occurringin either case.

Certainly ultrashort pulse laser ablation is used in a wide variety ofmaterial processing applications. However, the use of ultrashort pulselaser ablation of exposed cornea surfaces for clinical procedures islimited by several factors. An important limitation is the limits placedon input average power and input pulse energy to the cornea by safetyconsiderations associated with non-target tissues such as the retina. Asecond limitation is the requirements placed on the positioning of atightly focused laser spot at or near the target surface. Thislimitation in consideration of available practical ultrashort pulselaser sources results in micron precision in the positioning of thelaser focus with respect to the target tissue surface. It is a furtherlimitation that when positioning registration of a focused ultrashortlaser beam with respect to a target tissue surface is achieved, verysmall motion associated with the involuntary movements of the eye mayinterrupt tissue ablation before a meaningful volume of tissue can beablated.

Posterior Flap Ablation

The stromal surface targeted for laser ablation is created by manuallylifting and reflecting the anterior flap of tissue produced by blade orultrashort laser cutting. It is generally advantageous to target theexposed stromal bed for excimer laser ablation. In some excimer lasertreatments, it may be advantageous to target the posterior surface ofthe lifted flap instead of the stromal bed. For example, Maldonadoretreated LASIK patients by lifting a flap, manually marking the cornealflap anterior surface and manually directing an excimer ablation patternwith the laser keratome eye tracking system turned off (“Undersurfaceablation of the flap for laser in situ keratomileusis retreatment”,Ophthalmology Vol. 109, No. 8, August 2002). Maldonado marked theposterior flap surface with Gentian violent ink and a hand instrumentreferred to as a para-radial marker. He relied on visualizing the markedpattern and manually orienting the laser ablation pattern. He noted thata major challenge was stabilizing the eye and flap, and used handinstruments to stabilize the flap, relying on the reflected flap to lieon the eye anterior surface for the ablation. A limitation of theapproach of Maldonado is the poor stability of the reflected flap tissuesubject to laser radiation. A secondary limitation is the uncertainty inthe positioning of the flap posterior surface. These limitations areless important in the case of excimer laser pulse interaction, but areimportant in the potential use of tightly focused ultrashort pulses, afeature of my invention.

Eye Tracking and Corneal Marking

The corneal is usually marked for refractive surgery. In LASIK or otherlaser refractive surgery, hand instruments inked with Gentian violet oranother biocompatible dye are used to demarcate the corneal center, theoptical zone or other orientation information to facilitate thepositioning and placement of both the flap cutting keratome and theexcimer laser keratome instruments. Marking is typically done by hand orwith hand instruments. Marking is used to center and orient theplacement of microkeratomes or the placement of excimer lasertreatments. A typical hand instrument for marking the cornea inpreparation for laser refractive surgery is taught by Kritzinger in U.S.Pat. No. 5,752,967. Further examples of marking instruments may be foundin the extensive catalog of manual instruments available from KatenaProducts, Inc, Denville, N.J.

The biocompatible inks used for corneal marking can be oil-based orwater-based inks. Water-based inks—typically a formulation of Gentianviolet dye—do not bind strongly to the cornea. In fact, the water-basedink washes off quite easily, and tears, blinking or eye drops can easilyfade the markings before the laser procedure. For this reason, oil-basedinks are often preferred. According to Ide et al (“Effect of markingpens on femtosecond laser-assisted flap creation”, J Cataract RefractSurg 2009; 35:1087-1090), a limitation of oil-based inks is the tendencyfor the inks to interfere with the transmission of ultrashort orfemtosecond laser beams used to create corneal flaps. A furtherlimitation of oil-based inks is the difficulty of removing the inksafter the laser procedure is complete.

Laser surgery of the cornea requires precise placement of the laserpulses with respect to the location of the tissue surfaces. Voluntaryand involuntary movement of the eye relative to the laser beam opticalaxis may prevent the desired placement of pulses. Saccadic and slowerdrifts of the eye may be mitigated by instructing patients to fix theirgaze on a distant object or image. The human eye during directedfixation of the gaze exhibits three types of involuntary motion: tremor,microsaccades, and drifts (Physiology of the Eye, Dawson ed., page 663).These movements occur on several time and amplitude scales.Additionally, voluntary or reflexive motion may occur depending on thepatient's mental state and environmental stimuli. In corneal refractivelaser surgery a need exists to compensate for these movements. Theseapproaches are useful, but insufficient for precision laser surgery ofthe cornea by excimer lasers, and less useful in ultrashort pulsed lasersurgery of the cornea.

A mechanical means to restrain the subject eye may also be used.Restraining the eye generally requires pressure or low vacuum forces tobe applied to some part of the anterior portion of the eye globe. Theapplication of such forces can lead to discomfort, injury and surgicalcomplications. Additionally, restraining the eye is not sufficient forall eye motion.

A well-established feature of LASIK and other laser-based cornealrefractive surgeries is the detection of, and compensation for, eyemovements through the use of eye-tracking technology. Typically, eyetrackers employ multiple digital cameras to image high contrast anatomicstructures, such as the iris or the pupil edge. Software and firmwareprocessing of the images then produce image registration informationthat is used to track the motion of defined features. An early exampleof eye tracking for PRK was taught by Smith in U.S. Pat. No. 5,350,374.Eye tracking may be used passively or actively. Passive eye trackinghalts laser treatment when the eye motion ranges beyond an acceptablelimit. Active eye tracking continuously compensates for eye motion byre-directing the beam position and angle to match eye movement. Alimitation of eye tracking technology with respect to potential use inultrashort pulsed laser treatments is that the highest speed eyetracking technology available works in the kHz range, or has anequivalent bandwidth. Femtosecond lasers used to incise cornea nowoperate in the 100's of kHz range. The present invention optimally useslaser sources of pulse repetition rate above 1 MHz pulse repetitionrate. A limitation of the existing eye tracking art is that the speed ofeye trackers does not match the high repetition rates of ultrashortpulsed lasers that can perform clinically relevant ablation rates in anunrestrained cornea.

An alternative approach is the use of radar technology as in theLadarvision 4000, Alcon, Inc.

In ultrashort pulse corneal surgery, eye tracking is not performed. Thedistance tolerances for positioning the focused laser beam and thescanning path of the focus with respect to the corneal surface are high,and are typically on the order of a few microns. The invention taught byJuhasz in U.S. Pat. No. 6,254,595 uses an applanating optic incombination with a “skirt” that uses suction to apply a ring of suctionforce to the eye. This approach, essentially universal with ultrashortpulsed laser keratomes for corneal surgery, functions well for theincisional modality used presently by all commercial instruments.Applanating optics may be planar, as in the invention of Juhasz, or theymay have a curved surface conforming to the shape of the cornea. Thesesolutions work well for ultrashort pulsed laser incision cutting,because there is no need to allow material to be ejected from the targetsurfaces. A limitation of applanating devices is that direct ablationcannot be done at the same time. A means of placing tightly focusedultrashort pulsed laser pulses at targeted surface(s), with the targetedsurface(s) unobstructed, is needed to enable the ablation modality ofthe present invention.

Bille et al teach the use of laser-produced bubbles on the surface ofthe cornea to serve as tracking features for a laser-based trackingsystem in U.S. Pat. No. 4,848,340. One limitation of this invention isthe low contrast that a surface ablation feature on the cornea presents.A second limitation is the undesirability of introducing additionalinjuries or lesions to the surface of the cornea.

In U.S. Pat. No. 6,579,282, Bille et al teach the placement of bubblescreated inside the corneal stroma by laser photoablation, with thebubbles serving as guide features for image-based eye tracking systems.The bubble features for eye tracking are created rapidly by a scanninglaser, and may be created by an ultrashort pulsed laser. A limitation ofthis approach is the low contrast bubbles may present to eye trackingsystems. A second limitation is that laser-generated bubbles in stromadissolve and are resorbed in the corneal tissue over time. A thirdlimitation is the well-known phenomenon from ultrashort pulsed lasercorneal surgery in which bubbles created by laser vaporization in thecorneal stroma move along lamellar planes in unpredictable ways.

BACKGROUND OF THE INVENTION Objects and Advantages

Accordingly, in addition to the objects and advantages of the apparatusand methods described in my above patent, several objects and advantagesof the present invention are:

-   -   a) to provide a means of inducing a refractive change in the        human eye by direct removal of corneal tissue with ultrashort        pulsed laser ablation;    -   b) to provide a means for ablating stromal tissue on the        posterior surface of an exposed corneal flap with an ultrashort        pulsed laser;    -   c) to provide a means of allowing the use of high average power        and high pulse energy ultrashort pulsed laser beams to ablate        ocular tissue that exceed safe limits when used on an exposed        corneal stromal bed as in LASIK or related treatments;    -   d) to provide a means of producing ablation profiles of ocular        tissue of high spatial modulation;    -   e) to provide a means of ablating and thereby removing tissue        with small lateral dimensions as in an adhesion or tag of        corneal tissue;    -   f) to provide a means of removing sections of corneal tissue of        thickness smaller or more friable than can be safely removed and        cut by incisional means;    -   g) to provide a means of ablating ocular tissue with high pulse        rate ultrashort pulsed lasers that allows for relaxed positional        tolerances between target tissue and ablating beam;    -   h) to provide a means of ablating ocular tissue with high pulse        rate ultrashort pulsed lasers using an imaging eye tracking        system to compensate for involuntary motion of the eye;    -   i) to provide a means of incising or ablating ocular tissue with        ultrashort pulsed lasers without the need for an applanating        optic in contact with the cornea;    -   j) to provide a means of creating high contrast fiduciary marks        in cornea for use with an image-based eye tracking system;    -   k) to provide a means of creating fiduciary mark features in        human cornea with ultrashort pulsed laser incisions having        sufficiently small width so as to avoid interfering with visual        acuity of the patient;    -   l) to provide a means of creating fiduciary mark features in        human cornea with ultrashort pulsed laser incisions which can be        selectively impregnated with water-based dyes;

One advantage of the present invention is that a single laser platformmay be used to perform corneal refractive surgery, eliminating the needfor two separate and expensive laser systems. A further advantage isthat the invention may be used to create incisions and to directlyablate tissue to create a refractive effect, allowing a singleinstrument to perform many of the procedures presently performed byvarious laser and non-laser keratome instruments. A further advantage isthat the invention requires less direct contact with the eye relative toother ultrashort laser keratomes, offering the possibility of visioncorrection procedures that are less invasive than at present. Inparticular, some incisional procedures may be performed without the needfor an applanating optic in contact with the cornea. Such minimal touchsurgical procedures reduce the risk of infection, allow for greaterpatient comfort, and are associated with lower complication rates.

Further objects and advantages will become apparent from a considerationof the drawings and ensuing description.

SUMMARY OF THE INVENTION

In accordance with the present invention a refractive laser apparatuscomprises an ultrashort pulsed laser engine that produces a focusedscanning laser beam directed onto the human eye. The laser beam isguided by optical tracking subsystems. The present invention operates inboth an incisional mode to cut tissue and in an ablative mode to removetissue for purpose of correcting refractive errors in the human eye.

A method for producing high optical contrast fiduciary marks in biologictissue includes the steps of focusing short or ultrashort laser pulseson a cornea; scanning in a predetermined incisional pattern; and markingone or more incisions with the application of an optical contrast agent.The fiduciary marks are advantageous for optical tracking and motioncorrection of targeted tissue.

In an embodiment, the method also includes the step of verifying properfixation of a laser on a patient's eye prior to initiating the scanning.In an embodiment, an optical means is used to verify the proper fixationof the laser. In another embodiment, verifying proper fixation of thelaser comprises visualizing the patient's eye and the fiduciary marksand using a user-interface to determine an appropriate offset value.

In an embodiment, a width and a depth of the incisions is minimized toavoid interfering with visual acuity of a patient. In an embodiment, thewidth of the incisions is 1 to 30 microns, and the depth of theincisions is 10 to 100 microns. Optimally, the width of the incisions is5 to 15 microns, and the depth of the incisions is 20 to 50 microns.

In an embodiment, the incisions are made in a stromal bed that isexposed by cutting and lifting a corneal flap. In another embodiment,the incisions are made in a posterior surface of a corneal flap. In yetanother embodiment, the incisions are made on an anterior surface of thecornea.

In an embodiment, the contrast agent is applied by irrigating or wipingthe contrast on the one or more incisions. In an embodiment, the methodfurther includes the step of removing excess contrast agent from apatient's eye. The excess contrast agent is washed or dabbed away toleave a significant amount of agent in the incisions. Example contrastagents include, but are not limited to, biocompatible dyes, ophthalmicfluorescent dyes, biocompatible optical scattering agents, biodegradableagents, and biocompatible pigments.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, closely related figures have the same figure number,but have different alphabetic suffixes.

FIG. 1 is a representation of the invention performing a posterior flapsurface ablation surgical procedure

FIG. 2A is a top view of a representation of a single ablation disk incorneal tissue

FIG. 2B is a side view of a representation of a single ablation disk

FIG. 2C is a side view of completed representative ablation profile incornea

FIG. 3A shows both side and top view of exposed corneal stromal bed withlaser-cut fiduciary marks

FIG. 3B shows both side and top view of corneal stromal bed with singleablation disk completed

FIG. 3C shows both side and top view of stromal bed with multipleablation disks completed

FIG. 3D shows both side and top view of stromal bed with completedablation profile

FIG. 4A depicts side view of laser ablation process operating on exposedstromal bed

FIG. 4B depicts side view of post-ablation processes operating onexposed stromal bed

FIG. 4C depicts side view of repositioning of ablation assist arm afterablation sequence

FIG. 4D depicts side view of image acquisition step of surgical fieldfor use in optical tracking

FIG. 4E depicts side view of confocal optical signal acquisition forsensing z-position

FIG. 5A is a side view of creation of non-planar corneal flap forposterior surface ablation

FIG. 5B is a side view of non-planar corneal flap fixed on registrationplaten for posterior surface ablation

FIG. 5C is a side view of posterior flap surface ablation process

FIG. 5D is a side view of completed posterior flap surface ablationprocess

FIG. 5E is a side view of curvature change in cornea following posteriorflap surface ablation

FIG. 6 illustrates a preferred process flow for refractive procedureusing direct stromal bed ablation

FIG. 7 illustrates a preferred process flow for refractive procedureusing posterior flap ablation

FIG. 8A shows side view of incision and fiduciary mark cutting withanterior chamber anatomy

FIG. 8B shows expanded side view of laser incision and fiduciary markcutting

FIG. 8C shows side view of application of fiduciary mark contrast agent

FIG. 8D shows top view of completed stromal fiduciary marks withimpregnated contrast agent

DRAWINGS Guide to the Figures

FIG. 1 is a representation of the complete invention in the process ofperforming a refractive procedure in a preferred embodiment. Lasersource 200 is processed in optical processing module 210, passesscanning beam delivery module 220, and is coupled into focusing opticsmodule 230. Focusing optics module 230 focuses and impinges laser beam40 upon non-planar posterior flap surface 112 affixed to registrationplaten 120. Registration platen actuator module 262 actuates andpositions registration platen 120. Registration platen 120 containshydration manifold 126. Ablation assist arm 50 contains an aperture thattransmits focused laser beam 40. Ablation assist arm 50 actuates andpositions assist arm actuator module 260. Digital cameras 250 imageillumination rays 60 and relay images to processor 270. Axial positionsensing module 240 collects confocal signal from focusing optics module230 and relays signal to processor 270.

In FIG. 2A a single ablative disk 10 in tissue is shown. Ablative disk10 is shown as a disk consisting of a series of individual laserablation sites 12 arranged in a spiral produced by a scanning laserfocal spot. FIG. 2A shows the view from above the tissue, which ispreferentially corneal stroma, though other tissues may be ablated inother applications of the invention. FIG. 2B indicates ablation disk 10in schematic side view of corneal stroma 22, though other ocular tissuesmay be targeted. Characteristic depth 14 of ablation disk 10 may resultin a graded depth profile relative to the curvature of the exposedcorneal or stromal tissue surface 17. Ablation disk 10 hascharacteristic diameter 16, though for other shapes more than a singlevalue may characterize the lateral extent of the ablation feature. Otherablative feature geometries are possible, including a raster scan ofpolygonal geometry, annular rings, elliptical disks, and other planarshapes. The smoothness of the ablation disk is characterized by asurface roughness value that depends on the separation of individuallaser ablation shots 12, the separation of the shots and the values ofthe laser parameters used.

FIG. 2C depicts a completed ablation profile 11 located centrally inunablated tissue surface 17. Ablation profile 11 is created by placementof a series of ablation disks of diameter 16 with appropriatepositioning, overlap and depth. Design of ablation profile 11 can resultin a complex shape with distinct radius of curvature 13 and radius ofcurvature 15 characterizing the profile, and thereby the new refractivepower of the cornea. The minimum radius of curvature achievable inablation profile 11 is determined by the minimum horizontal overlap 18of ablation disk features and characteristic depth 14 associated with asingle planar ablation disk 10. Ablation profile 11 may also beconstructed with a highly localize geometry, for example, as may beoptimal for the removal of a small tissue adhesion or non-uniformity inthe cornea. Ablation profile 11 may also be constructed with highspatial modulation amplitudes to generate corrections for high orderaberrations.

FIG. 3 is a sequence in the tissue ablation process, with the tissuedepicted being human cornea. Both side and top views are shown.

FIG. 3A shows an exposed stromal bed 28 of a human cornea just prior tobeginning the ablation process. A top view of unaltered cornea 20 isshown at the top of the figure, while a side view of cornea crosssection 22 is shown at the bottom of the figure. An already-cut cornealflap has been lifted and reflected to expose the posterior surface 24 ofthe flap and the edge or side cut 26 of the flap. Fiduciary marks 30 areused to locate the ablation with respect to the correct optical axis(fiduciary mark fabrication is shown in FIG. 8A-D).

FIG. 3B depicts the side and top view of the exposed corneal stromal bedof FIG. 3A, with a single ablation disk 10 created at a first locationspecified by a computed ablation profile sequence of individual ablationdisks. Characteristic depth 14 of ablation of ablation disk 10 isindicated as a step in the stromal bed curvature at the bottom of FIG.3B.

FIG. 3C depicts side and top views of the exposed corneal stromal bed ofFIG. 3A after a number of ablation disks have been created at positionspre-determined by the requirements of the desired ablation profile.

FIG. 3D depicts side and top view of the exposed corneal stromal bed ofFIG. 3A after completion of ablation profile 11, which consists ofcomplete collection 19 of individual ablation disks 10.

FIG. 4 is a series of figures illustrating the ablation of cornealtissue as in FIG. 3, with the ancilliary processes that control andassist in the ablation process also shown.

FIG. 4A depicts a side view of cornea 22 with a flap already cut, liftedand reflected with corneal flap anterior surface 25 facing away from thefocused laser beam 40. Exposed stromal bed 28 already has a sequence ofablation disk features created, with creation of single ablation disk 10in process. Single ablation disk 10 is one in a sequence of scannedablation disks. Ablation assist arm 50 is mounted on a motion controlsystem integrated in the laser console (not shown). Aperture plate 52contains central aperture 51 that allows focused laser beam 40 to reachcorneal stromal bed 28.

FIG. 4B shows a side view of ablation assist arm 50 performing ablationassist processes. Nozzle 52 directs purge fluid 44 onto the localablation area associated with ablation disk 10. Purge fluid 44 mayconsist of pressurized air, water, saline, or other fluids or fluidsmixture compatible with biological tissue and useful for removing bypressure and direct contact any ablation products. At the same time, oralternatively, at a different time sequence, moisture or mist 42 may besupplied to the corneal tissue by hydration ports 56.

FIG. 4C shows a side view of the repositioning of ablation assist arm 50from position 58 to subsequent position 59. The repositioning ofablation assist arm 50 occurs in order to ready ablation assist arm 50for the next ablation disk in the planned sequence. The repositioningoccurs under motion control elements which center aperture 51 and otherassociated ablation assist features of ablation assist arm 50 over thenext target tissue location.

FIG. 4D shows a side view of a representative image acquisition step.Scattered illumination rays 60 originating from the surgical field areused by an image processing subsystem in the laser console (not shown inFIG. 4D) to analyze the relative lateral position of the laser opticalaxis with respect to the cornea.

FIG. 4E shows a side view of the acquisition of a confocal opticalsignal which locates the z-position or depth position of the focusedlaser beam relative to the target tissue surface. Confocal volume 71produces optical radiation that is collected as confocal image beam 70and relayed to detectors in axial position sensing module 240 (notdepicted in FIG. 4E).

FIG. 5 contains a series of graphics illustrating an embodiment in whichthe posterior surface of a non-planar corneal flap is ablated to producethe desired refractive change in the cornea.

FIG. 5A depicts a side view of a cornea that has had a non-planar flapcut by ultrashort pulsed laser incision. The flap cut containsnon-planar posterior flap surface 112 and planar posterior flap surface110. The non-planar flap cut may be performed with or without the use ofthe well-known applanating optics described in the art of femtosecondlaser keratomes. The peripherally located planar posterior flap surface110 is parallel to the corneal anterior surface, but non-planarposterior flap surface 112 has a curvature that is not parallel to thecorneal surface. Fiduciary marks 36 are produced as in FIG. 8, but withthe incisions being made in planar posterior flap surface 110 ratherthan in the stromal bed 116.

FIG. 5B shows a side view of the corneal flap of FIG. 5A now affixed toregistration platen 120. Registration platen 120 is connected to amicropositioning subsystem in the laser system (not shown) and can beused to move or position the flap in three translational dimensions withmicron-level precision. Registration platen 120 is connected to amicropositioning subsystem in the laser system (not shown) and can beused to move or position the flap in three translational dimensions withmicron-level precision. Registration platen 120 may also in someembodiments have the ability to gimbal or rotate the center of thecorneal flap with respect to one or more rotational axes to orient theposterior flap surface with respect to the ablating femtosecond beam 40.Registration platen interface 122 of registration platen 120 may be adisposable element. Registration platen interface 122 has a smoothcurved surface designed to match a typical human corneal surface. To aidin the mechanical fixation of the corneal flap on registration plateninterface 122, manifold 124 of low vacuum level may be integrated intoelement 122. Manifold 124 may be supplied with low suction force orvacuum from vacuum lines in registration platen 120 connected to thelaser system (not shown). Additionally, hydrating features 126 may wick,bleed or flow small amounts of physiologically appropriate fluid such asbuffered saline to the flap anterior surface. Hydrating features 126 maybe connected to a supply of fluid through a pump or reservoir of fluidin the console (not shown).

FIG. 5C illustrates a side view of the laser ablation step in posteriorflap ablation. Laser beam 40 is focused and scanned over non-planarposterior flap surface 112. An ablation profile is built up asillustrated in FIG. 2 and FIG. 3. Registration platen 120 may be used inconjunction with ablation assist arm 50 and ablation assist processesillustrated in FIG. 4.

FIG. 5D shows a side view of ablated posterior flap surface 130 of theposterior flap surface. Non-planar posterior flap surface 112 isdesigned and cut such that ablated posterior flap surface 130 results ina final posterior flap surface that is continuously parallel to theanterior corneal surface.

FIG. 5E shows a side view of the corneal flap after repositioning theflap onto exposed stromal bed 116. The result of the ablation ofnon-planar posterior flap surface 112 to yield ablated posterior flapsurface 130 is a corneal flap of uniform thickness, similar to the flapgeometry obtained in conventional microkeratome-generated corneal flaps.Ablated posterior flap surface 130 results in the corneal surfacerelaxing to a new position, giving rise to a new corneal shape 140 andrefractive power. Functionally, this is equivalent to creating a flap,and incising and removing a lenticule of the same shape. It is alsoequivalent to the stromal bed ablation process outlined in FIG. 8, butis produced with exposing the interior anatomy of the eye directly tothe ultrashort pulsed laser beam used for the ablation process.

FIG. 6 is a flow chart representing an embodiment of the invention, inwhich the process of producing a refractive correction in the human eyeis performed by initially exposing a stromal bed surface through thecutting and lifting of a planar corneal flap, and subsequently directlyablating the stromal bed surface through successive sequences of scannedultrashort pulsed laser patterns.

FIG. 7 is a flow chart representing an embodiment of the invention, inwhich the process of producing a refractive correction in the human eyeis performed by initially affixing the anterior surface of a cornealflap upon a registration platen thereby exposing the non-planarposterior surface of the flap, and subsequently by directly ablating theposterior surface of the corneal flap through successive sequences ofscanned ultrashort pulsed laser patterns.

FIG. 8 illustrates the creation of femtosecond laser cut fiduciary marks32 used to optically track the lateral position of the cornea withrespect to a subsequent femtosecond laser ablation process step. Allsequences of FIG. 8 are shown with the anterior chamber of the eye andcornea shown in cross section.

FIG. 8A shows a side view of cornea 22, the orientation of the anteriorsegment anatomy with respect to the focused laser beam 40, and theincisional paths associated with a flap cut and the creation offiduciary marks 32. Phakic lens 98 is attached to ciliary processes 96by zonule fibers 93. Iris structure 91 anterior to the lens 98 createspupil 97 at the posterior of humor-filled anterior chamber 95. Abovethese structures, cornea 22 is connected to sclera 94 by the limbus 92.The beam 40 is shown scanning across planned flap incision plane 82,having partially created flap incision 80. A separate scanning sequencehas produced side cut 84 to allow access to the flap with surgical handinstruments.

In FIG. 8B, an expanded side view from FIG. 8A is shown. The focalposition of the moving focused laser beam 40 results in individual andrapid photodisruption events 46. Photodisruptions 46 are created by theoptical breakdown that the femtosecond laser beam intensity produces.Secondary processes from the optical breakdown such as acoustic shockwave generation and propagation, cavitation bubble formation andoscillation and eventual localized tissue vaporization produce themicro-surgical effect of photodisruption in the same manner as is knownin the art associated with incisional femtosecond laser keratomes. Sidecut 84 is shown as a hashed line, as are already-cut flap incision 80and vertical fiduciary mark features 32. Planned flap incision 82 isshown as a dashed line. Incision 80, side cut 84, and fiduciary cuts 32may be cut using the invention in combination with the well-knownapplanation optics described in the prior art of femtosecond laserkeratomes. Alternatively, incision 80, side cut 84, and fiduciary cuts32 may be cut without an applanating optic using an eye motioncompensation system based on a lateral eye-tracking and z-positionconfocal sensor.

FIG. 8C shows an expanded side view of FIG. 8B after the flap (notshown) has been lifted from side cut 26 and exposing the interior ofcornea 22. Application of a contrast agent 102 is made on the exposedcornea interior using applicator 100. Fiduciary marks 30 have been dyed,marked or stained with the contrast agent 102. Excess contrast agent 101may be removed with irrigation or application of an absorbent wipe.

In FIG. 8D a top view is shown of the cornea in which the fiduciary markdyeing or staining process steps have been completed and fiduciary marks30 are visible with high optical contrast against the stromal bed 28.

DRAWINGS Reference Numerals

-   10 ablation disk pattern-   11 completed laser ablation profile-   12 single laser pulse ablation feature-   13 a first characteristic radius of curvature of laser ablation    profile-   14 ablation disk pattern characteristic depth-   15 a second characteristic radius of curvature of laser ablation    profile-   16 ablation disk characteristic diameter-   17 unablated/uncut corneal surface-   18 minimum overlap of adjacent disks-   19 collection of individual ablation disk features-   20 top view of corneal surface-   21 anterior chamber anatomy-   22 side view of cornea cross section-   24 flap posterior surface-   25 flap anterior surface-   26 flap side cut-   27 flap hinge-   28 exposed corneal stromal bed-   30 completed stromal fiduciary mark cut with contrast agent-   32 completed stromal fiduciary mark cut-   34 planned stromal fiduciary mark cut-   36 contrast agent dyed posterior flap fiduciary mark-   40 laser beam focal point-   42 hydrating mist-   44 purge gas or fluid-   46 photodisruption event at laser focus-   50 ablation assist arm-   52 aperture plate-   54 debris purge nozzle-   56 hydration port-   58 assist arm location for a specific ablation disk in sequence-   59 repositioned assist arm location for next ablation disk in    sequence-   60 large field image acquisition rays-   70 confocal rays to z-sensor-   71 confocal volume-   80 partially cut flap incision-   82 uncut flap incision path-   84 incision defining flap side cut-   91 iris anatomy of human eye-   92 limbus anatomy of human eye-   93 zonule fibers anatomy of human eye-   94 sclera anatomy of human eye-   95 anterior chamber anatomy of human eye-   96 ciliary processes anatomy of human eye-   97 pupil anatomy of human eye-   100 contrast agent applicator-   101 excess contrast agent layer-   102 contrast agent-   110 planar posterior flap surface-   112 non-planar posterior flap surface-   116 exposed stromal bed-   120 registration platen-   122 registration platen interface-   124 suction feature-   126 hydration manifold-   130 ablated posterior flap surface-   140 replaced flap with ablated posterior surface-   200 laser source-   210 optical processing module-   220 scanning beam delivery system-   230 focusing optics module-   240 axial position sensing module-   250 digital cameras-   260 assist arm actuator module-   262 registration platen actuator module-   270 processor

DETAILED DESCRIPTION OF THE INVENTION a) Overview of Invention

The present invention is an ultrashort pulsed laser keratome. Laserkeratomes are well known instruments for use in ophthalmic surgery.Ultrashort pulsed laser keratomes are generally used to create incisionsin the cornea. A typical use of an ultrashort pulsed laser kerartome isthe creation of corneal flaps in preparation for the vision correctingsurgical procedures known as laser assisted in-situ keratomileusis(LASIK).

The present invention performs incisions in a similar manner asfemtosecond laser keratomes, known in the art. Incisions in oculartissues are produced by ultrashort pulsed laser keratomes through thecreation of continuously connected patterns of individualphotodisruptions. Photodisruptions result from the phenomenon of opticalbreakdown, which results when the intensity at the focus of a laser beamexceeds the ionization breakdown threshold of the target material.Ultrashort pulsed laser keratomes produce patterns of photodisruptionsto create incisional surfaces, mimicking the action of a mechanicalblade.

The present invention similarly scans patterns of tightly focused laserpulses inside the volume of transparent ocular tissue, or in a preferredembodiment, on the exposed surface of an ocular tissue such as cornea.The invention may be used to create incisions in this manner. Theinvention also performs direct refractive corrections through anablative mode, not known in the art.

FIG. 1 depicts a preferred embodiment of the invention. Referring toFIG. 1, I now point out several major elements of the present invention.Laser source 200 generates a high repetition rate beam of laser pulses.Preferably, the pulses have pulse energies of 1-20 microJoules. Thepulses are optimally less than 1 picosecond in duration. Optimal pulserepetition rates are at least 1 MHz.

The laser beam generated in laser source 200 is processed in opticalprocessing module 210. Optical processing module 210 provides beamconditioning, beam shaping, beam energy monitoring, and other opticalprocessing of the picosecond or femtosecond pulse train. Theconditioning of the beam in optical processing module 210 results in abeam of characteristics suitable for launch into scanning beam deliverysystem 220. Techniques for shaping and monitoring ultrashort pulsedlaser beams are well-known to those skilled in the art of picosecond andfemtosecond lasers.

Referring again to FIG. 1, the ultrashort pulsed laser beam is routedinto scanning beam delivery module 220. Scanning beam delivery module220 contains high speed rotary scanners, such as galvanometric motors.The scanners in module 220 and the associated optics output a beam ofcontinuously varying angle. The angular variation is designed to matchthe requirements of focusing optics module 230. Focusing optics module230 produces focused laser beam 40 which impinges on the target oculartissue. In a preferred embodiment, the target tissue is affixed toregistration platen 120. Focusing optics module 230 also converts theangular variation in the input beam into a precision translation of thefocus. High speed and continuous variation of the beam launch angleexiting focusing optics module 230 produces a continuously moving pathof the focus of laser beam 40. The moving path of focused laser beam 40may be designed to produce continuous patterns of individual laserpulses. Such an arrangement is known to those skilled in the art as anf-theta lens arrangement. Other approaches to produce a similar scanningfocus are known in the art.

Patterns of scanned laser pulses are produced in target ocular tissue byscanning beam delivery system 220 in combination with focusing opticsmodule 230. The patterns written by scanning beam delivery system 220are advantageously designed to create a particular two-dimensional orthree-dimension shape in the tissue. Incisional surfaces consist of manythousands or millions of micron-scale photodisruption events.

In a preferred embodiment, registration platen 120 affixes and maintainscorneal flap surface at a controlled position. In FIG. 1, a corneal flaphas been cut and lifted from anterior chamber of the eye anatomy 21 in aprevious step of the surgical process. Non-planar posterior flap surface112 is oriented to the focused laser beam 40 by registration platen 120.Registration platen 120 has a precision curved surface designed toconform to the anterior corneal surface, facilitating the orientation ofnon-planar posterior flap surface 112. Registration platen 120 alsocontains hydration manifold 126. Hydration manifold 126 applieshydrating fluid to the anterior corneal surface. Hydration manifold 126also applies a low suction force to the anterior surface of the cornealflap, with the terms “anterior” and “posterior” corresponding tostandard medical nomenclature.

The suction force and hydration fluid are supplied by registrationplaten actuator module 262. The suction force applied by hydrationmanifold 126 is sufficiently low to release flap in the event ofmovement.

Registration platen actuator module 262 also provides precisionthree-dimensional positioning control to registration platen 120.Processing control of registration platen actuator module 262 isperformed by processor 270.

Ablation assist arm 50 assists in the ablation process. Ablation assistarm 50 is positioned proximate to exposed non-planar posterior flapsurface 112. Ablation assist arm 50 contains an aperture that transmitsfocused laser beam 40. Ablation assist arm 50 provides purge fluid toassist the ablation of target tissue. Ablation assist arm 50 alsoprovides hydration fluid to the target tissue. Ablation assist arm 50 isconnected to assist arm actuator module 260. In a similar fashion to thefunctioning of registration platen actuator module 262, assist armactuator module 260 supplies hydration fluid, purge fluid and precisionmotion control to ablation assist arm 50. Assist arm actuator module 260positions ablation assist arm 50 in response to the commands fromprocessor 270. The position of ablation assist arm 50 is determined bythe particular location of an ablation sequence being executed. Ablationassist arm 50 is nominally centered over the target ablation site on anexposed tissue surface, for example, the exposed non-planar posteriorflap surface 112 in FIG. 1.

In a preferred embodiment, the invention also includes an opticaltracking system. Referring again to FIG. 1, one possible opticaltracking system is shown. Digital cameras 250 capture images of thesurgical field from illumination light rays 40 emanating from thesurgical field and relay the captured images to processor 270. Imageprocessing techniques, well known in the art, are used to constructdifference information between consecutively acquired images. Relativelateral motion of the surgical field, for example, of non-planarposterior flap surface 112, is computed. Focused laser beam 40 may beadjusted to compensate for the detected motion. Alternatively,registration platen actuator module 262 may be commanded by processor270 to reposition the corneal flap to compensate for the detectedmotion.

Other lateral optical tracking systems known in the art, such aslaser-based systems, may be employed in other embodiments of theinvention.

In a preferred embodiment, the invention also includes an axial positionor depth optical sensing system. Axial position sensing module 240 inFIG. 1 detects the position of the tissue interface by the measurementof light intensity collected from the confocal volume of focusing opticsmodule 230. The source of the confocal signal may be the laser itself,or may alternatively be supplied by coherent or incoherent illuminationsource in optical processing module 210. The size of the signal detectedby axial position sensing module 240 is proportional to the distancebetween the tissue interface and the position of the focusing opticsmodule 230. Dithering the focal position or the position of the tissueinterface allows for a determination of the position of the interface tobe made by software in processor 270. Alternatively, a computingprocessor may be located for this purpose in axial position sensingmodule 240. Alternatively, other optical-based approaches known in theart may also be used for the axial position sensing module.

b) Ablation Disks

Ablation of tissue in the present invention occurs through thephotodisruption of tissue at or near an exposed or free surface uponwhich focused laser beam 40 impinges. The invention ablates oculartissue by performing successive, stacked sequences of short durationablation patterns. An individual ablation pattern or ablation sequencewill be referred to as an ablation disk.

In the ablative mode of the present invention, the applanation andmechanical fixation features used in conventional femtosecond laserkeratomes are not useful, applanation and mechanical fixation featuresmay be advantageously used in alternative embodiments of the invention.Ocular tissues targeted for ablation preferably have an exposed and freesurface.

In FIG. 2A a single representative ablative disk 10 in tissue is shownin top view. Ablative disk 10 is shown as a disk consisting of a seriesof individual laser ablation sites 12 arranged in a spiral produced by ascanning laser focal spot. FIG. 2A shows the view from above the tissue,which is preferentially corneal stroma, though other tissues may beablated in other applications of the invention.

FIG. 2B indicates ablation disk 10 in schematic side view of cornealstroma 22. Characteristic depth 14 of ablation disk 10 may result in agraded depth profile relative to the curvature of the exposed corneal orstromal tissue surface 17. Ablation disk 10 has characteristic diameter16, though for other shapes more than a single value may characterizethe lateral extent of the ablation feature. Other ablative featuregeometries are possible, including a raster scan of polygonal geometry,annular rings, elliptical disks, and other planar shapes. The smoothnessof the ablation disk is characterized by a surface roughness value thatdepends on the separation of individual laser ablation shots 12, theseparation of the shots and the values of the laser parameters used.

A number of patterns of individual ablation sequences may be used.Optimally, small diameter circular disks of spiraling lines ofconsecutive pulses are used. A preferred disk ablation pattern is shownin FIG. 2A. An individual ablation disk is optimally planar. Depthgradation of the overall ablation process is determined by the overlapand placement of disks of varying depth, that is, disks that are scannedat various positions along the optical axis or depth axis. During theactual laser ablation process, ablation sequences are overlaid in a waythat the “islands” and edges of the ablation features overlap to resultin a smoothly increasingly deep ablation profile.

An individual ablation disk diameter is determined by the repetitionrate of the laser, the linear scanning speed and the amount of timeallowed for an individual ablation sequence (itself determined by thetime scale of the fixated eye motions), and by the desired spatialfrequency and surface smoothness of the final ablation profile. FIG. 2Bshows an ablation disk 10 of characteristic roughness <r>, where <r> isof the order of ablation disk characteristic depth 14.

c) Ablation Profiles

FIG. 2C depicts a completed ablation profile 11 located centrally inunablated tissue surface 17. Ablation profile 11 is created by placementof a series of ablation disks of diameter 16 with appropriatepositioning, overlap and depth. Ablation disks 10 are arranged accordingto a predetermined ablation profile that depends on the desiredrefractive correction, following the prescriptions of Munnerlyn (U.S.Pat. No. 5,163,934) or other refractive correction algorithms known inthe art. Geometric calculations are used to create the ablationprescription in advance of the procedure. The calculated ablationprofile uses the input of the desired refractive change and initialcorneal topography and shape diagnostic information supplied byclinicians prior to the procedure.

The design of ablation profile 11 can result in a complex shape withdistinct radius of curvature 13 and radius of curvature 15characterizing the profile, and thereby the new refractive power of thecornea. The minimum radius of curvature achievable in ablation profile11 is determined by the minimum horizontal overlap 18 of ablation diskfeatures and characteristic depth 14 associated with a single planarablation disk 10. Ablation profile 11 may also be constructed with ahighly localize geometry, for example, as may be optimal for the removalof a small tissue adhesion or non-uniformity in the cornea. Ablationprofile 11 may also be constructed with high spatial frequency orspatial modulation to generate corrections for high order aberrations.

A minimal amount of time is allowed between each ablation disk 10 forthe beam scanners to reposition for the production of the next ablationdisk.

In this manner, creating ablation profile 11 is similar to theoverlapping performed by large spot ablations performed in excimer or UVlaser ablation of corneal tissue in LASIK. More generally, creatingablation profile 11 resembles the well-known process of overlappinglaser pulses for machining a broad range of materials. In conventionallaser processing of materials, the relatively shallow ablation depth ofan individual laser pulse allows for overlapping and stacking of pulsesto create a smooth, blended ablation profiles with some freedom todesign the overall ablation profile, depending on the laser pulsecharacter, and the ablation characteristics of single laser pulses inthat material system. In the present invention, the sequence of laserpulses making up ablation disk 10 are similar to the individual, largearea single pulses used in the conventional laser material processingexample discussed above.

FIG. 3 illustrates the development of ablation profile 11 through thecumulative placement of collected ablation disk features 19. FIG. 3Ashows an exposed stromal bed 28 of a human cornea just prior tobeginning the ablation process. A top view of unaltered cornea 20 isshown at the top of the figure, while a side view of cornea crosssection 22 is shown at the bottom of the figure. An already-cut cornealflap has been lifted and reflected to expose the posterior surface 24 ofthe flap and the edge or side cut 26 of the flap. FIG. 3B depicts theside and top view of the exposed corneal stromal bed of FIG. 3A, with asingle ablation disk 10 created at a first location specified by acomputed ablation profile sequence of individual ablation disks.Characteristic depth 14 of ablation of ablation disk 10 is indicated asa step in the stromal bed curvature at the bottom of FIG. 3B. FIG. 3Cdepicts side and top views of the exposed corneal stromal bed of FIG. 3Aafter a number of ablation disks have been created at positionspre-determined by the requirements of the desired ablation profile. FIG.3D depicts side and top view of the exposed corneal stromal bed of FIG.3A after completion of ablation profile 11, which consists of completecollection 19 of individual ablation disks 10.

Producing ablation of ocular tissue by stacking or layering many smallablation disks has at several advantages.

An important advantage is that a series of small ablation disks can bestill be created even though useful ablation rates require a very highlinear scan rate. As discussed in a later section of this application,the linear speed of the focal spot exceeds 1 m/s. Since ablation disks10 have spiral geometries, the volume of ablation disk 10 can be tracedby scanning beam delivery system 220 operating at or near the maximumlinear rate. At the same time, the ablation profile can be executed insmall increments, so that micron-level precision during the entireablation process is not necessary. If the entire scanning sequence wereperformed continuously, as it is in existing femtosecond laserkeratomes, the requirements for positioning the tissue with respect tofocused laser beam 40 would be onerous. A trade-off in performing manysmall ablation disk ablation operations is that scanning beam deliverysystem 220 repeatedly repositions focused laser beam 40, which takes upvaluable scan time. In order to minimize the intervals between ablationdisk scans, ablation disk 10 characteristic diameter 16 is optimallyless than 1 mm.

A second advantage is that the precision tolerance used for positioningconsecutive ablation disks 10 can be relaxed relative to the precisiontolerance used for positioning of consecutive laser pulses within aparticular ablation disk. That is, the error in the positioning ofconsecutive ablation disks can be much larger than the error in thepositioning of consecutive laser pulses within an ablation disks. Forexample, placement of a particular 1 mm diameter disk may be associatedwith a lateral tolerance of +/−50 microns, while the placement of twosuccessive laser pulses within that disk may be 3 microns+/−1 micron.The tolerance or precision with which successive laser pulses may beplaced partially determines the characteristic surface roughness withwhich ablation profile 11 can be produced.

Ablation profile 11 is arrived at by the design of the pattern ofoverlapping ablation disks 10. The tolerance or precision with whichsuccessive ablation disks can be placed partially determines the size ofthe amplitude modulation that ablation profile 11 may have. A relativelyrelaxed lateral tolerance of +/−50 microns between consecutive ablationdisk placements allows for an amplitude modulation of ablation profile11 comparable with what can be achieved with small spot excimer laserablations.

The flexibility in designing ablation profiles 11 may be used to performablative treatments to remove small areas. In particular, tissueadhesions may be ablated, such as may be created in an unsuccessfulmanual or incisional maneuver that leaves behind small bits of tissue.Additionally, high order optical errors may be corrected by ablationprofiles that require high spatial modulation amplitudes. In otherwords, the lateral extent of a particular ablation zone can be of smalldimensions. Features having lateral dimensions that approximate thediameter of ablative disk 10 may be ablated or removed. Such featuresmay measure as small as 0.5 mm across.

d) Motion Compensation

Ablation is performed on exposed corneal or ocular surfaces that areunconstrained in a preferred embodiment. Motion occurring in the subjecteye or cornea be compensated for or otherwise mitigated in order tofacilitate an efficacious ablation process.

The human eye during directed fixation of the gaze exhibits three typesof motion: (1) tremor, (2) microsaccades, and (3) drifts. During activevision, other motions occur, such as vergence or large scale saccades,etc. (Physiology of the Eye, Dawson, ed. page 663).

The drift contribution is quite slow, taking many seconds, but haverelatively large amplitude motions. Drifts may result in severalarc-minutes of angular motion, but are easily compensated for bytracking and repositioning scanners between ablation sequences, in whichan individual ablation sequence occurs in a burst of time that is on thescale of tens of milliseconds.

Microsaccades occur more rapidly, with high angular speed at irregularintervals of ˜1 second. The angular speed is such that the microsaccadewill likely cause the ablation sequence to be incomplete or erroneous.However, for the high speed at which the ablation sequences areperformed (also tens of milliseconds in duration), the microsaccadicmotions will only occasionally cause errors in the ablations, and can becorrected for by repeating zones during which a microsaccade occurs, orby updating the ablation profile algorithm to account for the error. Theoptical tracking sub-system is used in a preferred embodiment toidentify ablation disk 10 sequences in which the positional errorexceeds a threshold tolerance value. The ablation profile algorithm issubsequently updated to compensate for the particular incompleteablation disk flagged as exceeding the threshold tolerance. Preferredprocesses for performing refractive corrections are outlined in the flowcharts in FIG. 6 and FIG. 7. Error checking for such out-of-toleranceablation disks is explicitly part of a preferred method or processoutlined in these flowcharts.

Tremor motion occurs more frequently, though at much smaller amplitudes.The rate of tremor is 30-70 Hz, with amplitudes of up to 20 arc-seconds.The largest amplitude motion corresponds to ˜1 micron of lateralmovement at the corneal surface. Most tremor individual tremor motionsare small enough that they do not have to be compensated or adjustedfor. If the integrated motion exceeds a few microns during an ablationdisk scanning sequence, the motion is optimally compensated for bysubsequent ablations of that area as outlined in the precedingparagraph.

Large scale eye motions, such as non-fixated saccades, or voluntary orinvoluntary change of gaze or eye positions will result in the treatmentbeing temporarily or permanently halted.

The primary reason for creating an ablation profile 11 by a series ofdiscrete ablation disks 10, rather than by continuously tracking andcompensating for relative motion is that the linear speed of the focusedlaser beam 40 linear speed and the laser repetition rate are very high.These high rates exceed practical limits associated with opticaltracking, micropositioning and data processing. The present inventionhandles these challenges in a novel way through the step-wisefabrication of discrete ablation disk 10 features sized to avoid mosteye motions. Errors in ablation disk 10 fabrication are dynamicallyupdated in the ablation profile algorithm.

For example, in an optimally sized photodisruption event 46 depicted inFIG. 8B, the resulting ablation feature size in corneal tissue maymeasure approximately 2 microns in lateral extent. If the entireablation sequence to produce a refractive change were performed in acontinuous scan, the lateral optical tracking and motion compensationrequirement to maintain good registration of the ablation duringscanning would require an approximately 2 micron tolerance on trackingand positioning accuracy. This requirement would make any ablation modedifficult and inaccurate.

1) Error Correction

In the present invention, the ablation process requires precisepositioning of both consecutive laser shots and the placement ofconsecutive ablation disks. The size of an individual laser shotablation is on the micron scale. Fabrication of ablation profilesrequires that the tissue removed in such a way that minimal amount ofincompletely ablated material lies between consecutive laser shots, andalso between consecutive scan lines.

Saccadic or other eye motions may cause relative motion between thefocused laser beam 40 and a particular target tissue location. If thenumber of incomplete, interrupted or erroneous ablation sequencesaccumulated exceeds a tolerable value, the ablative process can bepaused or halted to correct conditions causing unacceptable relativemotion of the eye. Low patient compliance or inadequate fixation maycause such motion.

Position errors above a critical size are detected by the opticaltracking and axial position sensing functions of the invention. Ifmotion exceeding an allowed tolerance value is detected during aparticular ablation sequence, the position and parameters associatedwith the particular ablation disk scan sequence are used to dynamicallyupdate the calculated ablation profile algorithm. The algorithm isupdate to successfully ablate the region or zone in which the positionerror occurred, or to compensate for the unsuccessful ablation byadjusting other aspects of the ablation profile algorithm. Incomplete orerroneous ablation disk sequences can be repeated, ignored, or overlaidwith subsequent ablation disks.

As an example consider a series of ablation disks with sequence numberspresenting by integers n, m and p. Following the unsuccessful completionof a particular ablation disk number [n], the next planned disk [n+1]may be executed as planned, and the unsuccessful disk ablation [n]repeated before proceeding to disk [n+2]. The pattern of disk ablationsis then resumed until the final disk ablation N is reached.Alternatively, the error in disk number [n] may be noted, and severalplanned disks [n+1] through [n+m] completed. Then, using an adjustedablation pattern, the volume of tissue at the location of the originallyplanned disk [n] is removed in a sequence of ablation disk [n+m+1]through [n+m+p]. After this detour in ablation sequence, the originalremaining disks beyond number [n+m] are completed.

2) Mechanism for Motion Compensation

Motion compensation during ablation occurs as a result of opticaltracking of lateral relative motion and optical sensing or ranging ofone or more points on the corneal surface in the axial or depthdirection. Referring back to FIG. 1, lateral position optical trackinginformation obtained through tracking digital cameras 250 may be used tore-direct the internal scanning elements of scanning beam deliverysystem 220 relative to focused laser beam 40. Alternatively registrationplaten 120 may be re-positioned relative to focused laser beam 40,thereby translating the position of the non-planar posterior flapsurface 112 relative to focused laser beam 40. In an alternativeembodiment, both corrections may be applied to optimize the motioncompensation response. Axial position information obtained by axialposition sensing module 240 may be used to re-direct the internaltranslating elements of focusing optics module 230 relative to thenon-planar posterior flap surface 112.

3) Optical Tracking

FIG. 4D shows a side view of a representative image acquisition step.Scattered illumination rays 60 originating from the surgical field areused by an image processing subsystem in processor 270 (from FIG. 1) toanalyze the relative lateral position of the laser optical axis withrespect to the cornea.

In an alternative embodiment, high bandwidth tracking allows fortracking, re-positioning and error tracking at speeds exceeding thefrequency of the eye, known to be less than 70 Hz. The preferablebandwidth of the tracker enabling individual tremor tracking optimallyfollows approximately the Norquist statistical criteria for signalsampling. Therefore the desired bandwidth of a suitable tracking systemoptimally exceeds approximately 250 Hz. For example, the iView XHi-Speed system from SensoMotoric Instruments GmbH has an adequatemaximum acquisition rate of 1250 Hz. A custom image processor isefficacious to achieve the real-time bandwidth requirement forcontinuous positioning correction.

4) Axial Position Sensing

Tracking of lateral relative motion is performed in a preferredembodiment of the invention using digital image capture, imageprocessing, and image registration. A separate requirement for thepresent invention is precise tracking of the axial position of thetarget ablation surfaces with respect to the position of the focus oflaser beam 40. A preferred method for measuring and controlling theposition of the laser focus is a confocal optical arrangement. A probeoptical beam is focused at a point or points on the target surface usingfocusing optics module 230. Scattered or reflected light from the targetsurface is re-imaged by focusing optics module 230 and redirected by abeamsplitter onto a photo detector in axial position sensing module 240.The photodetector signal is a maximum when the target tissue surface islocated within the depth of focus of this confocal optical arrangement.The photodetector signal may be advantageously used to modulate thefocusing power of the ablating ultrashort pulsed laser beam by suitablyactuating optical elements of focusing optics module 230.

The focusing power of focusing optics module 230 is arranged to provideappropriate axial depth or z-position sensitivity. Optimally, the depthof focus is set to equal or exceed the precision requirements foroptimal an ultrashort pulsed laser tissue interaction, namely surfaceablation. The resulting confocal axial sensitivity is then equal to orsmaller than the Rayleigh range of the ultrashort pulsed focused beam,which is optimally 3 microns or smaller. The confocal arrangement issimilar to many used in confocal microscopy and related techniques.

In an alternative embodiment, a confocal arrangement may be used incombination with a wavelength shift in the probe light beam.Autofluorescence or fluorescence from an contrast agent applied to thetarget tissue surface provides the detected signal collected from thetarget tissue surface. As is well known in the art, wavelength shiftingof confocally collected probe light is advantageous due to thenon-linear dependence of the wavelength conversion on the probe beamintensity. A confocal arrangement with wavelength shiftingadvantageously increases the sensitivity of the dependence of theoptical signal on the axial position.

FIG. 4E shows a side view of the acquisition of a confocal opticalsignal which locates the z-position or depth position of the focusedlaser beam relative to the target tissue surface. Confocal volume 71produces optical radiation that is collected as confocal image beam 70and relayed to detectors in axial position sensing module 240 (from FIG.1.)

5) Timing Considerations

Tremor motion amplitude is sufficiently small that conventional videoframe rate eye trackers may be used in an alternative embodiment.Although tremor motion occurs at frequencies exceeding typicalbandwidths of video frame rate eye tracking systems, the invention maybe advantageously used to create ablation disks without correction ofmotion during each ablation disk sequence, as previously described. Inone embodiment, conventional video frame rate bandwidth trackers (25-30frames/sec) are used in parallel to the ablation disk sequences.

In one embodiment, time intervals between ablation sequences areincluded in the ablation process to allow for: (i) determination byimage-based tracking of the lateral position of the target tissuesurface with respect to the laser optical axis; (ii) determination ofthe axial or depth position of the target tissue surface, most optimallyby a sensitive confocal beam detecting the interface between the tissuesurface and air, most optimally in a non-ablated region of the cornea,and potentially at multiple sites, (iii) removal of ablation debris by aburst or continuous purge fluid jet directed at or near the ablationsite, (iv) an optional process step of hydrating the corneal surface bya mist, aerosol spray or hydration fluid jet. In a preferred embodiment,the features tracked by the lateral image tracking function arefiduciary marks created using the invention in a previous step.Fiduciary mark creation is described below.

In another embodiment, conventional trackers are used, but the trackingoccurs at the end of each ablation disk sequence, and the ablation disksequences lengths are designed to match the tracking speeds. In order toexecute a surgical procedure as rapidly as possible, individual ablationdisks are scanned with approximate scan duration times corresponding tovideo frame rates. Timing intervals between consecutive ablation disksequences are optimally small in comparison to the time to complete asingle ablation disk scan sequence. For example, a 25 fps (frames persecond) conventional video tracker may be used to acquire images at 40millisecond (msec) intervals with an image acquisition window width of 5msec, and a re-positioning window width of 5 msec, with ablationsequences lasting 30 msec. In this example, 10 msec total is allowed forablation assist processes (described below), if those processes aretimed to occur between ablation sequences. The relatively short 5 msecrepositioning window may be used to place the scanners into positionassuming no motion during the acquisition time. If a positioning errorresult during the ablation disk creation step, the particular ablationdisk may either be halted or allowed to complete, and the position ofthe erroneous ablation recorded and folded into the prescription for theremaining ablation sequences. A reasonable duty factor for ablation diskcreation process of 75% is thus achieved, allowing for the bulk of thetotal laser procedure time to be dedicated to actual tissue ablation.The repositioning and acquisition times are optimally only a fraction ofthe “on time” of the laser ablation sequences to allow for the mostrapid procedure times.

Axial position sensing module 240 operates in parallel to the lateraleye tracking function. The timing of axial sensing may advantageous beperformed in a similar manner as the eye tracking function. Axialposition sensing is important because the position of the laser focus isoptimally be axially with a precision greater than the depth of focus ofthe laser beam, which optimally is less than 10 microns, and is moreoptimally less than 2 microns.

6) Fiduciary Marks for Optical Tracking

In excimer laser treatments known in the art, lateral tracking of theiris or pupil is commonly used to control an excimer laser beam or haltthe excimer laser beam if the relative motion exceeds a threshold value.In a preferred embodiment of the present invention, the reference pointsand features to be optically tracked are fiduciary marks laser cut intothe cornea. Laser-cut fiduciary marks may be advantageously impregnatedwith biocompatible contrast agents to improve the performance of theoptical tracking function. Laser-cut fiduciary marks are described indetail below.

In an alternative embodiment, un-ablated and un-cut surfaces of thecornea may be used as reference features for the optical trackingfunction.

In a preferred embodiment, the optical paths used for lateral trackingand z-position tracking are shared by the laser beam focusing andscanning objective lens. Alternative embodiments may use a paralleloptical path or paths, as would be clear to one skilled in the art.

e) Theory of Operation—Ablation

The present invention operates by producing controlled optical breakdownevents in ocular tissue. Each optical breakdown event results in a setof secondary phenomena known as photodisruptions. The phenomena ofphotodisruption include: shock wave generation, shock wave propagation,localized tissue vaporization, gas vapor bubble expansion, and gasbubble cavitation. These are well-known physical processes that havebeen advantageously used in other laser keratomes. Photodisruptions actin a small volume highly localized to the location of the opticalbreakdown. Ultrashort pulse photodisruption events in ocular tissue aretypically 1-100 microns in extent, depending on the particular laserparameters and tissue properties involved.

As is well known in the art, femtosecond and picosecond laser keratomesuse photodisruption to produce incisions in ocular tissue such ascornea. Both an incisional mode and an ablative mode are realized in thepresent invention. However, a novel aspect of the invention is toperform refractive surgery by direct ablation of tissue using ultrashortpulsed laser photodisruption at or near a tissue surface. Ablation isnot used by ultrashort pulsed laser keratomes known in the prior art.

Enabling features for the ablative mode of the invention include: (i)high bandwidth lateral optical tracking; (ii) depth-sensitive opticaltracking of the axial position of the target tissue; (iii) ablationprofile patterns based on overlays of ablation disk scan patterns, saidablation disk scan patterns being sufficiently rapidly performed so asto in the main avoid pattern disruption by the larger amplitude naturalmotions of the eye; (iv) fabrication of fiduciary marks on or in thecornea to enable lateral optical tracking independent of the eye anatomyand unaffected by the ablation process; and (v) apparatus for holding,registering and conditioning a corneal flap to allow ablation of theposterior surface of the flap. Various embodiments of the invention mayuse some or all of these enabling features in combination.

A description of the theory of ablative operation is therefore shownbelow.

1) Ablation Volumes

Optical breakdown and photodisruption are arranged to occur at or near atissue surface exposed to air and to the impinging focused laser beam40. Material is ejected from the free surfaces targeted by impingingfocused laser beam 40. Repeated scanned patterns of laser pulses mayremove a specific volume of tissue to create a refractive effect.

The zone of tissue affected by a superficial application of an optimalpulse is deeper than the nanosecond excimer pulses used in commercialrefractive laser keratomes. Additionally, the lateral zone of ablatedtissue associated with a single laser pulse is measured in a few micronsrather than the approximately 1 millimeter width associated withrefractive lasers such as are used in so-called flying spot excimerlasers. Lateral in this sense refers to the planar dimensions parallelto the corneal surface. A zone of tissue ablated through opticalbreakdown and associated processes by such a pulse would optimally be avolume of a few microns across and 1 micron or less deep. It isadvantageous that the depth of an individual pulse or application ofpulses at a particular surface be small compared to the optical powerassociated with the removal of a layer of corneal tissue of the samethickness. A beneficial pulse may produce an individual ablation featuremeasuring 1 micron deep with a lateral radius of 1 micron, with a volumeof approximately 3 cubic microns.

In order to make useful the small ablation features produced by theinvention, a large number of pulses are preferably rapidly applied in ashort time to remove a useful volume of tissue. To estimate the numberof laser shots to complete a clinical procedure, consider the well-knownMunnerlyn formula predicting the size of a lenticular section of corneato be preferably removed in order to make a refractive correction. For amyopic correction, a lenticular volume of approximately

˜⅓*(R zone)̂2*CT

is to be removed. R zone is the radius of the optical zone and CT is thecentral and thickest part of the lenticular piece of tissue to beremoved. For a relatively large correction of 10 diopters, typicalexemplary values may be used: R zone=3 mm; CT=100 microns.

The resulting lenticular volume to be removed in this example isapproximately 3×10̂8 cubic microns. If the pulses are assumed to ablatethis volume with 100% efficiency, using an approximate value of 3 cubicmicrons/laser shot for the volume ablated in a single pulse, anestimated 1×10̂8 individual pulses would be used. However, in reality asignificant overlap of individual pulses is preferable to produce asmooth ablation profile. An effective ablation efficiency of 30% or lessrelative to the theoretical ablation efficiency associated with thesingle pulse ablation volume value used above. Therefore, the samevolumetric tissue removal requirement for an exemplary 10 dioptercorrection above may require as many as 3×10̂8 individual pulses. Thepresent invention may advantageously complete the ablation of thisvolume in a clinically reasonable time, for example, 100 seconds. Theapproximate laser repetition rate estimated in this example is thenapproximately 3 MHz.

Some incisional femtosecond laser keratomes presently marketed achievesuch high laser repetition rates. For example, the Ziemer LDV system(Ziemer Ophthalmic Systems AG) operates at up to 2 MHz, though at muchlower average power than the present invention. The LDV maximum averagepower is approximately 100 nanoJoules*2 MHz=200 milliWatts. The LDV andother laser keratomes operate only in an incisional mode.

2) Scanning Performance

Another aspect of the invention is the requirement for high beamscanning rates. Using the example parameters from above, the estimatedlateral separation of adjacent laser focal spots is optimallyapproximately 1 micron. A typical linear rate of scanning thataccurately places consecutive laser spots at this separation requires awell-controlled linear speed of 3 m/s, though rates between 1 and 10 m/smay be advantageously used.

This high rate of linear scanning may be performed in several ways. Themost advantageous way is the use of a large field high numericalaperture F-theta scanning objective lens. This method is well known inthe art of laser scanning, and is commonly used in femtosecond laserkeratomes. The F-theta lens is a laser scanning lens in which the imageheight, or rather the lateral location of the focal spot, isproportional to the product of the laser beam entrance angle withrespect to the optical axis (theta, or θ) and the lens focal length F.That is, the spot position is proportional to the product F*θ, ratherthan the usual value for conventional lenses of F*tan θ. The linear scanrate for such an F-theta is then linearly dependent on the angular speedof the incoming beam, rather than the usual dependence of angular scanrate for an ordinary lens of the quantity d/dt[tan θ]. This is generallyaccomplished with appropriate lens design that includes the correctamount of optical distortion in the lens to produce the F*θ dependenceof the focal spot position.

linear scan speed˜ω*F

-   -   where ω=dθ/dt is the angular sweep speed of the input laser beam

Galvanometric (galvo) motor rotation rates as 1000 radians/sec arepreferable for high linear spot speeds.

The timing intervals between scans of consecutive ablation disks 10 mayrequire duty cycle factors of 75% or more.

To achieve a high angular rate, a high torque and angular speedgalvanometric or other electromechanical motor devices are used to driverelatively small diameter mirrors, optimally 1 cm diameter or smaller.Optical processing module 210 conditions the laser beam to match thebeam diameter and beam divergence to properly fit on the smalldeflection mirrors in scanning beam delivery system 220. The angularlydeflected, small diameter beam is then expanded in an optical telescopeor equivalent in focusing optics module 230 and launched into a highnumerical aperture (NA) F-theta scan lens, or into a similar fieldscanning lens. The angle of the input beam with respect to the lensoptical axis determines the position of the focal spot, and thereforethe incision cutting point or ablation point of the femtosecond beam.

3) Free Surface for Ablation

There is a requirement in femtosecond laser keratomes known in the art,and also in the present invention, that the scanned laser pulses areplaced regularly and continuously so that scan spots and scan lines canbe laid precisely together. Further, the laser scans are preferablyrapid enough that clinical procedures can be performed in an acceptableamount of time. The preferred method for producing scans both rapidlyand with high precision uses a spiral scan. Spiral scans allow theangular scanning speed to be continuously high, while the smallincrement in the spiral radius allows for good control of the placementof consecutive scanning lines. The latter point is important becauseerrors in precision due to the scanning or motion that occurs add up todegrade the incisional quality. Incisional femtosecond laser keratomesuse mechanical fixation and an applanation optic to maintain preciseregistration between the cornea and the scanning optical axis.Femtosecond laser keratomes are frequently assisted by the use of a lowvacuum or suction limbal suction ring that temporarily attaches bysuction to the corneal periphery or the limbus. In these keratomes,incisions are created in the corneal stroma, with the laser beam passingthrough an applanating contact optic. The contact glass serves as aprecision reference surface for the scanned laser beam, and alsoimmobilizes the cornea. Typically, the applanating contact optic is usedto maintain lateral and axis stability of the cornea with respect to theincident cutting laser beam.

While applanation with a applanating contact optic works well forincisional procedures, performing ultrashort pulsed laser ablation withan applanating contact optic is problematic. Material ablated at thesurface of the cornea or other ocular tissue may be trapped between theablation zone and the applanating optic. The result would be acombination of optical blocking of subsequent laser pulses by trappeddebris, adhesion of debris to the target tissue/substrate, anddeposition of unwanted heat back into the bulk material from trappedablation ejecta. Ablation is optimally performed with the target tissuesurface to exposed or free.

The invention may also be used partly or wholly without requiring thelimbal suction fixation rings often employed by femtosecond laserkeratomes known in the art.

On the other hand, in performing ablation with ultra-violet (UV)wavelength lasers, such as the excimer lasers used in LASIK procedures,applanation of the cornea is not necessary. Applanation is not necessaryin UV ablation of the cornea because the control of the z-position ofthe laser beam with respect to the target tissue surface is notparticularly important. The ablating UV beam is not focused, but israther collimated. Tissue ablation performed with these lasers occursindependently of the axial location of the ablation surface with respectto the laser beam. Ablation by such a laser beam occurs wherever thebeam intersects the target absorbing material, viz., corneal stroma.This is because the ablation occurs due to the linear absorption of thecollimated beam, and does not depend on a tightly converging beam, as isarranged in the present invention. Put another way, an ablating UV beampropagates until it strikes the cornea, where it is strongly absorbedand creates ablation of a particular depth that depends linearly on thefluence of the incident beam.

In order to produce tissue ablation with high precision and limitedcollateral damage, the size of an individual ablation event is optimallyof extent from one to several microns in size. This is achieved in thepresent invention with tightly focused ultrashort laser pulses appliedat or near a surface to be ablated, with parameters chosen to produceoptical breakdown at or just below the target surface.

4) Wavelength

Transparency of the target tissue is the principal concern in choosing awavelength for the invention. The transparency window of ocular tissuefrom approximately 700 nm to 1100 nm is an acceptable range. Theinvention preferentially uses wavelengths between 1000 nm and 1100 nm.

5) Pulse Duration

As is known in the art, photodisruption of ocular tissue by ultrashortpulsed lasers may usefully be performed below pulse durations of 10picoseconds. Pulse durations of less than about 1 picosecond optimallyproduce deterministic and localized photodisruptions. Pulse durations ofabout less than 50 femtoseconds are unnecessarily difficult to manage inoptical designs. The invention therefore preferably uses pulse durationsless than 1 picosecond and greater than 50 femtoseconds.

6) Focusing

As previously described, ultrashort pulsed laser beams may beadvantageously arranged to produce optical breakdown and photodisruptionof tissue. Properly chosen parameters localize effects immediatelyproximate to the focus of the laser beam. A focused scanning femtosecondbeam impinging on a transparent tissue does not produce any absorptionin target tissue until the fluence exceeds a threshold value. Thethreshold value for optical breakdown is controlled by the focusingproperties of the beam, as well as by controlling the laser beam pulseparameters. This allows for the unique interaction properties exploitedby femtosecond laser keratomes known in the art, such as the ability toproduce localized effects at a precise point in three dimensions,without affecting surrounding tissue.

Control of the focal position with respect to the target location isoptimally precisely controlled, preferably on the scale of one micron.This is usually achieved through the use of an applanating contactoptic. With the present invention, an applanating contact optic may ormay not be used in the incisional mode. In the ablation mode, noapplanation glass is used. Ablation is performed by the invention uponexposed ocular tissue or corneal stroma surfaces.

Therefore, the invention preferably corrects or compensates for relativemotion of the eye and target tissue surfaces with respect to focusedlaser beam 40 in three dimensions. The motion compensation requirementsare determined in part by the beam focus requirements. Typically, focusdepth of a laser beam is described by the Rayleigh range parameter,which is defined as the axial distance over which the beam diameterincreases from the minimum value at the laser focus by a factor thatresults in a doubling of the spot area. For a Gaussian laser beam, thisis related to the focal spot radius:

Z _(Rayleigh)=pi*(focal spot radius)̂2/lambda

For an advantageously sized spot diameter of 1.5 microns and awavelength of 1.064 nm, the Rayleigh range is approximately 1.7 microns.The desired precision in the depth or axial position of the focal spotis related to the Rayleigh range, viz., preferably less than 5 micronsand optimally to within 1 micron.

7) Pulse Energy

In the present invention, the preferred extent or length scale of thelaser-tissue is between one and several microns. The pulsed energy usedper laser is preferably not large in comparison to the optical breakdownthreshold in order to achieve this size of tissue interaction. Inpreferred embodiments, the invention may produce optical breakdownevents using pulse energies between 0.1 and 1 microJoules. To limit thefeature size of a single laser-tissue interaction, the energy per pulseis optimally less than about 10 times the optical breakdown thresholdenergy, and as small as practicable. The preferred pulse energy range ofthe invention is therefore between about 1 and 20 microJoules, andpreferably between 1 and 10 microJoules.

8) Average Power

Ablation of corneal tissue, whether using the present invention or someother means, is optimally rapid enough to perform a clinical procedurein a short period of time. Acceptable procedure times for the actualmaterial ablation step are 1 minute or less. To achieve thisperformance, the high average power ultrashort pulsed laser beam of theinvention is optimally scanned at a high linear rate of speed across thetarget cornea surface(s).

Additionally, using the volumetric ablation rates estimated above, lasersource 200 of the invention preferably operates between 1 and 10 MHz,and used between 1 and 10 microJoules per pulse. The inventionpreferably uses between 1 and 100 Watts of average power, and optimallyused between 1 and 10 Watts of average power.

The average power of present invention is between 1 and 2 orders ofmagnitude higher than is used in femtosecond laser keratomes known inthe art. The delivered average power optimal for the direct ablation ofa clinically meaningful amount of cornea is significantly higher thanwould be used to simply incise or cut cornea. The invention may beswitched between incisional and ablating modes, enabling a singleinstrument to create a corneal flap or other incisional feature, andthen to ablate tissue to produce the desired refractive effect. In theincisional mode, the invention preferentially uses between 100milliWatts and 1 Watt of average power.

g) Ablation Assist Features

In the ablative mode of the invention, ablated material may accumulateas debris on surfaces proximate to the target tissue. Such debris mayimpede the ablation process. The debris is advantageously removed by gasor fluid purging, in a process that is similar to processes well knownin the art of laser material processing. In the present invention, theablation debris is biological tissue rather than metal or othermaterials commonly removed by air, liquid or other fluidic jet orpurging streams known in the art. Purging functionality is integratedinto ablation assist arm 50.

An additional process of replacing moisture from the surrounding orunderlying tissue may be desirable. A humidity supplying element or awater-aerosolizing element may be employed to continuously direct mist,humidity or vapor at the tissue in order to maintain physiologichumidity. Such an element may consist of a platen surrounding the tissuesubject to ablation at a close distance, and may consist of a rigidmember with a through hole that allows the laser and other optical beamsto reach the corneal tissue. Alternatively, direct contact with amoisturizing surface in contact with the anterior surface of the cornealflap may be used. The moisturing surface may be integrated withregistration platen 120, and may consist of a series of irrigation poresor micropores in registration platen 120.

FIG. 4A depicts a side view of cornea 22 with a flap already cut, liftedand reflected with corneal flap anterior surface 25 facing away from thefocused laser beam 40. Exposed stromal bed 28 already has a sequence ofablation disk features created, with creation of single ablation disk 10in process. Single ablation disk 10 is one in a sequence of scannedablation disks. Ablation assist arm 50 is mounted on a motion controlsystem integrated in the laser console (not shown). Aperture plate 52contains central aperture 51 that allows focused laser beam 40 to reachcorneal stromal bed 28.

FIG. 4B shows a side view of ablation assist arm 50 performing ablationassist processes. Nozzle 52 directs purge fluid 44 onto the localablation area associated with ablation disk 10. Purge fluid 44 mayconsist of pressurized air, water, saline, or other fluids or fluidsmixture compatible with biological tissue and useful for removing bypressure and direct contact any ablation products. At the same time, oralternatively, at a different time sequence, moisture or mist 42 may besupplied to the corneal tissue by hydration ports 56.

FIG. 4C shows a side view of the repositioning of ablation assist arm 50from position 58 to subsequent position 59. The repositioning ofablation assist arm 50 occurs in order to ready ablation assist arm 50for the next ablation disk in the planned sequence. The repositioningoccurs under motion control elements which center aperture 51 and otherassociated ablation assist features of ablation assist arm 50 over thenext target tissue location.

Both the purging step and the humidifying step may be performed by theinvention at intervals or continuously, depending on the particularablation parameters. The assist processes of debris purging andhydration may occur in parallel to the ablation sequences, andcombinations of sequential and parallel assist steps may beadvantageously employed.

h) Posterior Flap Ablation

An alternative embodiment avoids ablation of the exposed stromal bed infavor of ablating the posterior surface of a corneal flap. The flap maybe created by incision with the ultrashort pulsed laser, or bymechanical or other means. An advantage of ablating the posteriorsurface of the flap is that the interior of the globe itself is notexposed to laser radiation. In conventional LASIK or other laserrefractive procedures, the corneal stromal bed and the interior of theeye are directly exposed to UV laser radiation. Replacing the UVablating laser with direct exposure of the eye interior to the highaverage laser power of the present invention may result in a hazardousexposure of eye structures to thermal or other energy. An advantageousembodiment of the invention is used to perform ablation upon themechanically reflected and exposed posterior surface of a pre-cutcorneal flap. This method avoids harmful radiation or thermal effectsfrom laser exposure to the interior of the eye.

1) Non-Planar Posterior Flap

In an embodiment of the invention, an initial non-planar flap shape iscut in such a way that subsequent ablation of the flap produces a finalflap geometry that is planar. A non-planar flap may be cut by theincisional mode of the present invention, by a commercially availablefemtosecond laser keratome, or even by a specialized mechanical bladekeratome. Using the incisional mode of the present invention, acircularly symmetric but non-planar flap cut may be made by changing thedepth of the focal point continuously and slowly as the spiral cuttingof the flap is performed.

FIG. 5A depicts a side view of a cornea that has had a non-planar flapcut by ultrashort pulsed laser incision. The non-planar flap cutcontains non-planar posterior flap surface 112 and planar posterior flapsurface 110. The non-planar flap cut may be performed with or withoutthe use of the well-known applanating optics described in the art offemtosecond laser keratomes. Peripheral located planar posterior flapsurface is parallel to the corneal anterior surface, but non-planarposterior flap surface 112 has a curvature that is not parallel to thecorneal surface. Fiduciary marks 36 are produced as in FIG. 8 (describedbelow), but with the incisions being made in the posterior surface ofthe planar posterior flap surface 110 rather than in stromal bed 116.

2) Registration Platen

In the posterior flap ablation embodiment of the invention, a feature toregister, hold and manipulate the flap tissue is preferably used. Thefeature, referred to as registration platen 120 in FIG. 5B, fixes theposterior surface with respect to the ablating ultrashort pulsed laserbeam 40 with a high degree of precision and steadiness.

Registration platen 120 is depicted in FIGS. 5B and 5C. Registrationplaten 120 performs several functions: (i) to mechanical hold anteriorflap surface 25 onto precision registration platen interface; (ii) toprovide a means for mechanically translating or rotating the cornealflap in three dimensions to optimize the orientation of non-planarposterior flap surface 112 to the ablating laser beam; (iii) to providethe appropriate level of physiologic hydration to the flap tissuebefore, during and after the ablation process; and (iv) to provide alaser absorption and thermal sink for the appreciable fraction ofincident laser power which passes through the tissue withoutcontributing to the optical breakdown and ablation process.

FIG. 5B shows a side view of the corneal flap of FIG. 5A now affixed toregistration platen 120. Registration platen 120 is connected toregistration platen actuator module 262 (FIG. 1) and provides precisionthree-dimensional positioning control to registration platen 120.Registration platen 120 may also in some embodiments have the ability togimbal or rotate the center of the corneal flap with respect to one ormore rotational axes to orient the posterior flap surface with respectto the focused laser beam 40. Registration platen interface 122 ofregistration platen 120 may be a disposable element. Registration plateninterface 122 has a smooth curved surface designed to match a typicalhuman corneal surface. To aid in the mechanical fixation of the cornealflap on registration platen interface 122, manifold 124 of low vacuumlevel may be integrated into element 122. Manifold 124 may be suppliedwith low suction force or vacuum from vacuum lines in registrationplaten 120 connected to the laser system (not shown). Additionally,hydrating features 126 may wick, bleed or flow small amounts ofphysiologically appropriate fluid such as buffered saline to the flapanterior surface. Hydrating features 126 may be connected to a supply offluid through a manifold and further connected to a pump or reservoir offluid in the console (not shown).

The suction force and hydration fluid are supplied by registrationplaten actuator module 262. The suction force applied by hydrationmanifold 126 is sufficiently low to release flap in the event ofmovement.

FIG. 5C illustrates a side view of the laser ablation step in posteriorflap ablation. Laser beam 40 is focused and scanned over non-planarposterior flap surface 112. An ablation profile is built up asillustrated before in FIG. 2 and FIG. 3. Registration platen 120 may beused in conjunction with ablation assist arm 50 and ablation assistprocesses illustrated in FIG. 4.

FIG. 5D shows a side view of ablated posterior flap surface 130 of theposterior flap surface. Initial non-planar posterior flap surface 112 isdesigned and cut such that ablated posterior flap surface 130 results ina final posterior flap surface that is continuously parallel to theanterior corneal surface.

FIG. 5E shows a side view of the corneal flap after repositioning theflap onto exposed stromal bed 116. The result of the ablation ofnon-planar posterior flap surface 112 to yield ablated posterior flapsurface 130 is a corneal flap of uniform thickness, similar to the flapgeometry obtained in conventional microkeratome-generated corneal flaps.Ablated posterior flap surface 130 results in the corneal surfacerelaxing to a new position, giving rise to a new corneal shape 140 andrefractive power. Functionally, this is equivalent to creating a flap,and incising and removing a lenticule of the same shape and volume. Itis also equivalent to the stromal bed ablation process outlined in FIG.4, but is produced with exposing the interior anatomy of the eyedirectly to the ultrashort pulsed laser beam used for the ablationprocess.

The control of the depth or axial dimension may be advantageouslycontrolled by translating registration platen 120, by altering theposition of focused laser beam 40, or a combination of the two methodsfor optimal control of the ablation depth in tissue.

In an alternative embodiment, optical tracking is not dynamically usedduration ablation, since the position of non-planar posterior flapsurface 112 can be maintained and controlled in three dimensions bymovement of registration platen 120 with respect to focus laser beam 40,once the correct initial position of the flap has been obtained. Opticaltracking may be used to obtain the initial correct position of the flapin this alternative embodiment.

It should be clear to the reader that other pre-cut flap geometries andablation profiles 11 may be advantageously used by the invention. Forexample, an ablation profile of the posterior flap surface may result ina flap that is not planar after the ablation process is complete.

In an alternative embodiment, combined curvatures ablated in bothexposed stromal bed 116 and in non-planar posterior surface 112 tocreate a desired refractive change.

In yet another alternative embodiment, ablation of non-planar posteriorsurface 112 is arranged to produce ablation profiles to perform myopicor hyperopic corrections.

In yet another alternative embodiment, ablation of non-planar posteriorsurface 112 is arranged to produce non-circularly symmetric ablationprofiles to perform astigmatic corrections, or to create othernon-spherical or higher order refractive error corrections.

3) High Average Power Ablation

The high average power to ablate corneal and ocular tissue in anacceptably short time may exceed safe limits for retinal and thermalexposures. For example, an optimal 10W average power beam of femtosecondlaser pulses used a preferred embodiment of the invention to ablatetissue for a clinically acceptable duration of 60 seconds results in anapproximate 600 J laser energy exposure to the interior of the eye. Suchan exposure is obviously unacceptable. The use of posterior flap surfaceablation avoids such exposures. In a preferred embodiment, high averagepower ablation is enabled by this method and device because the totalexposure of laser power or energy in direct stromal ablation wouldotherwise represent a hazardous laser radiation exposure to the subjecteye.

i) Exemplary Process Flows

One embodiment of the invention may be used to perform a cornealrefractive procedure that resembles a LASIK procedure. In a first step,the invention is used to produce a conventional corneal flap.Alternatively, other instruments, including mechanical blade basedmicrokeratomes, may be used to create the flap. In a second step, anablative portion of the corneal refractive procedure is replaced withthe ablative mode of present invention. An ablation profile 11 isperformed as previously described. Ablation profile 11 is constructed toresembled the ablation nomograms produced by an excimer laser ablation,for example, as may be used in a so-called “flying spot” excimer laserLASIK procedure. In analogy to the excimer procedure, each flying spotmay be considered as a single spiral scanned ablation disk 10 previouslydescribed. The ablation disk features 10 are placed with the aid of ahigh bandwidth three dimensional optical tracking apparatus, which in apreferred embodiment uses a set of laser cut and contrast-agent dyedfiduciary marks to serve as the optical contrast tracking features.

FIG. 6 presents a detailed procedure flow for this embodiment.

Another embodiment of the invention is the performance of a cornealrefractive procedure using the previously described technique ofposterior flap ablation.

FIG. 7 presents a detailed procedure flow for this embodiment.

j) Theory of Operation—Incisions

Conventional ultrashort pulsed laser keratome incisions, such as cornealflaps, lamellar keratoplasties, penetrating keratoplasties, relaxingincisions, and other incision shapes may obviously be realized by theinvention.

The incisional mode of the present invention is similar to that ofcommercially available femtosecond laser keratomes.

In a preferred embodiment, incisions may be created without using anapplanating contact optic, through the use of optical tracking orientedby laser-cut fiduciary marks.

In an alternate embodiment, well known methods in the art of femtosecondlaser keratomes may be used to create incisions. These methods include,but are not limited to: use of a means of mechanical or suction fixationof the eye; use of a contact optic to applanate the eye; and the use ofan applanation optic to serve as a reference surface for focused laserbeam 40.

k) Fiduciary Marks

Optical tracking is optimally performed by imaging features having goodoptical contrast and that represent a fixed reference surface locatesthe target tracking object is located in two or more dimensionals ofposition and rotational space. In refractive excimer laser system andophthalmic diagnostic devices known in the art, the pupil of the eye isoften used as a reference. However, the pupil is not a fixed reference.The pupil can dialate or move under accommodation, other ocular motionsor under the influence of intraocular pressure changes.

Retinal trackers are used for some purposes, though they cannot be usedto track or control the corneal surfaces in the present invention, sincethere is a significant separation and possible deformation between thefront and back portions of the eye.

A preferred method is to use a feature in the anterior chamber, and morepreferably to use the cornea itself. However, the cornea is transparentand offers little optical contrast. The corneal surface may be manuallymarked using a surgical marking pen with an ink, dye or stain. It isadvantageous, however, to create optical marks or features with awell-defined spatial relationship to the visual axis of the patient'seye. It is further advantageous to create such marks with a well-definedfeature size, geometry and contrast because of the high precisionpreferred for the tracking and motion correction to precisely performthe incision and ablation maneuvers of the present invention.

The present invention combines several elements to create high contrast,precision features for optical tracking referred to as fiduciary marks.The first element is the common method of directing the patient to gazefixedly at a known object in order to establish fixation of the eye. Thesecond element is visualization of the patient eye by the physician oroperator through viewing optics or a relayed video image of the eye toverify proper fixation of the patient gaze. The third element is thecutting of predefined incisional patterns using the ultrashort pulsedlaser into or onto the cornea. The forth element is the staining, dyeingor marking of the surfaces containing the incisions by the applicationof appropriate contrast agent or agents. The fifth element is thesubsequent washing or rinsing of the tissue surface containing incisionsto remove excess contrast agent.

Fiduciary marks may be created in a single sequence with the creation ofother incisions, such as flap generation. Fiduciary marks may also becreated separately from other cuts. Fiduciary marks may be located onthe posterior surface of a corneal flap, on the stromal bed underneaththe flap, or may be on the anterior surface of the otherwise uncutcornea.

The fiduciary mark cutting itself optimally occurs very rapidly so thatat the moment of best patient fixation, the pattern of cuts is laid inwithout motion of the eye. Once the fiduciary mark cuts have beenproduced, the tissue where the fiduciary mark cuts are located isaccessed, either directly at the corneal surface or by lifting aultrashort pulsed laser flap cut. The contrast agent is applied byirrigation, wiping or other means. Excess contrast agent is washed ordabbed away to leave a significant amount of agent trapped, stained,bound or otherwise localized in the array of incisions. The agents maybe simple biocompatible dyes, such as Gentian violent, indocyanine green(IDG), brilliant blue G, Bengal rose. The agents may also be ophthalmicfluorescent dyes, such as fluorescein or rhodamine based dyes. Theagents may also be biocompatible optical scattering agents,biodegradable agents, biocompatible pigments such as melanins.

Importantly, fiduciary marks are created with dimensions that are largeenough to be advantageously impregnated with the applied contrast agent,but small enough that the agent is easily dispersed over time. Thedimensions are also advantageously chosen to minimize effects on humanvision. In particular, the widths and depths of the marks are optimallysmall. Preferred fiduciary mark kerf widths are between 1 and 30microns, and preferably between 5 and 15 microns. Preferred fiduciarymark depths are between 10 and 100 microns, and preferably between 20and 50 microns.

FIG. 8 illustrates the creation of femtosecond laser cut fiduciary marks32 used to optically track the lateral position of the cornea withrespect to a subsequent femtosecond laser ablation process step. Allsequences of FIG. 8 are shown with the anterior chamber of the eye andcornea shown in cross section.

FIG. 8A shows a side view of cornea 22, the orientation of the anteriorsegment anatomy with respect to the focused laser beam 40, and theincisional paths associated with a flap cut and the creation offiduciary marks 32. Phakic lens 98 is attached to ciliary processes 96by zonule fibers 93. Iris structure 91 anterior to the lens 98 createspupil 97 at the posterior of humor-filled anterior chamber 95. Abovethese structures, cornea 22 is connected to sclera 94 by the limbus 92.The beam 40 is shown scanning across planned flap incision plane 82,having partially created flap incision 80. A separate scanning sequencehas produced side cut 84 to allow access to the flap with surgical handinstruments.

In FIG. 8B, an expanded side view from FIG. 8A is shown. The focalposition of the moving focused laser beam 40 results in individual andrapid photodisruption events 46. Photodisruptions 46 are created by theoptical breakdown that the femtosecond laser beam intensity produces.Secondary processes from the optical breakdown such as acoustic shockwave generation and propagation, cavitation bubble formation andoscillation and eventual localized tissue vaporization produce themicro-surgical effect of photodisruption in the same manner as is knownin the art associated with incisional femtosecond laser keratomes. Sidecut 84 is shown as a hashed line, as are already-cut flap incision 80and vertical fiduciary mark features 32. Planned flap incision 82 isshown as a dashed line. Incision 80, side cut 84, and fiduciary cuts 32may be cut using the invention in combination with the well-knownapplanation optics described in the prior art of femtosecond laserkeratomes. Alternatively, incision 80, side cut 84, and fiduciary cuts32 may be cut without an applanating optic using an eye motioncompensation system based on a lateral eye-tracking and z-positionconfocal sensor.

FIG. 8C shows an expanded side view of FIG. 8B after the flap (notshown) has been lifted from side cut 26 and exposing the interior ofcornea 22. Application of a contrast agent 102 is made on the exposedcornea interior using applicator 100. Fiduciary marks 30 have been dyed,marked or stained with the contrast agent 102. Excess contrast agent 101may be removed with irrigation or application of an absorbent wipe.

In FIG. 8D a top view is shown of the cornea in which the fiduciary markdyeing or staining process steps have been completed and fiduciary marks30 are visible with high optical contrast against the stromal bed 28.

In another embodiment, fiduciary marks are created on the portion of thecornea outside of planned femtosecond cut or ablation zones in theprocess flow of FIG. 6, and as shown in FIG. 3 and FIG. 4.

In another embodiment, fiduciary marks are created on posterior flapsurface outside of planned femtosecond cut or ablation zones in theprocess flow of FIG. 7, and as shown in FIG. 5.

l) Combined Modes

The invention may combine the use of fiduciary mark features, incisionalmodality and ablative modality. For example, the invention may be usedto cut a corneal flap and then be used to subsequently perform anablative refractive procedure.

The invention may be used to perform incisional operations with orwithout the use of applanating contact optic. If an applanating contactoptics is used, fiduciary marks may be initially created, then markedwith a dye or contrast agent, then utilized by the eye trackingsubsystem to correct for eye motion, with or without subsequentapplanation. If applanation is not used, fiduciary marks may still becreated. In either of these two cases, centration of the laser beam withrespect to the patient visual axis may be performed by instructing thepatient to fixate at an optical target, which may be corrected for theparticular patient's refraction. The physician may use optical means forverifying proper fixation prior to initiating the laser scan sequencethat creates the fiduciary marks. The fiduciary mark scans may beperformed very rapidly so that the marks are created at precisely thecorrect moment of best fixation. This step may be important in that thefiduciary marks provide information that the invention uses to createrefractive incisional and ablative features. These features would resultin refractive errors if the fiduciary marks used to center them resultedin a decentering error. An additional step of verifying the centrationof the fiduciary marks may be used in which the physician visualizes thepatient eye and the selectively dye-stained fiduciary marks and uses theuser-interface to record in the system software an appropriate offsetvalue.

In another embodiment, the method of producing optically trackablefiduciary marks in the cornea may be performed to enable completelydistinct subsequent procedures or techniques that are neither refractivesurgery or ultrashort pulsed laser procedures. In other words, thecreations of fiduciary marks may be used for other surgical ordiagnostic procedures for which the determination of the visual axis ofthis eye is important.

m) Other Embodiments 1) Finishing Cuts

Side effects associated with the use of femtosecond laser keratomes areknown to include “transient light sensitivity syndrome”, and diffuselamellar keratitis. It has been reported that these and other surgicalcomplications may be associated the use of high energy pulses.

The present invention may be used advantageously to first performablative refractive procedure using relatively high energy pulses, andthen to complete the procedure by ablating the final layers of tissueremoved using substantially lower laser energy. The ablation efficiencyof the overall surgical procedure is not substantially affected becausemost of the tissue ablation occurs at high laser energies. Unwantedtissue damage or tissue effects performed at high energy are avoidedbecause the final thickness of tissue removed was performed at a lowerenergy. Such an approach is similar to how mechanical machining of amaterial surface is performed with conventional steel tools. I thereforerefer to the use of the present invention to perform final ablationsusing low pulse energies as “finishing cuts”. Finishing cuts performedin this way have other advantages, including creating intrinsicallysmoother surfaces than would occur if high pulse energies were used.

2) Topographically Planned Ablation

In an alternative embodiment, the procedure described in FIG. 5 and FIG.7 may be performed without active optical tracking or axial positionsensing. Topographic mapping of the cornea may be used as input to thedetermination of the ablation profile algorithm. After an initial stepin positioning a pre-cut flap on registration platen 120 with respect tofocused laser beam 40, the invention may execute the ablation profilealgorithm “blindly”, relying on the known position of registrationplaten and the previous knowledge of the corneal topography. Similarapproaches will be obvious to one skilled in the art. For example, asimilar mapping of the cornea may be performed using wavefront analyzersand used as input information for the determination of the ablationalgorithm.

3) Lenticules and Tissue Adhesions

As in known in the art, femtosecond laser keratomes may be used to cut astromal lenticule to be extracted from the cornea to produce arefractive change. The present invention may also be used tosimultaneously cut a flap and a stromal lenticule to be extracted fromthe cornea through the flap,

In the lenticule procedure as performed presently by femtosecond laserkeratomes, a small amounts of adherent tissue resulting from themechanical removal of the lenticule can result in significantdegradation of the visual outcome. The present invention may be used tofollow up the incision and removal of the lenticule with a customablation of the tissue tags or adherent tissue. This approach enablesthe removal of unwanted tissue tags, stromal fragments or other smallscale defects in cornea or corneal stroma, that cannot be performed bythe surgeon with sufficient precision or reliability.

CONCLUSIONS, RAMIFICATIONS AND SCOPE OF INVENTION

Thus the reader will see that the laser apparatus of the inventionprovides a means of producing corneal refractive surgery through directablation of ocular tissue. The invention may also be used to performcorneal incisions in the fashion of other ultrashort pulsed laserkeratomes. Optical tracking and laser-cut fiduciary marks in oculartissue assist in the ablative performance of the laser apparatus. Thereader will also see that the method of producing refractive correctionsallows for the advantageous use of a single instrument, eliminating theneed for two separate surgical instruments.

The description of the invention above contains many examples andspecifications for clarity. These examples and specifications are notintended to limit the scope of the invention. For example, in theablating modality, ablation features other than circular planar disksmay be employed, such as planar annular rings, non-planar disks, ornon-planar thin strips. In another example, two different pulse widthlaser beams may be used to produce the incisional cuts and the ablativetissue removal in order to advantageously operate the laser instrumentin different pulse regimes.

The present invention is also a general method for ablation of oculartissues. For example, non-corneal tissue may be ablated and the opticaltracking and high speed ultrashort pulsed laser beam may beadvantageously used to produce ablation of ocular tissue such as sclerafor the creation of sclerotomy features in the treatment of glaucoma. Inanother example, the ablative mode may be used for the ablation andremoval of lens tissue for the treatment of cataracts or presbyopia.

Another alternative use of the invention may be the ablative removal ofdermal tissue for cosmetic or dermatologic treatments such as skincancer treatments.

The present invention allows high power ultrashort pulsed laser ablationof tissue that may exhibit uncompensated or uncontrolled small motionswith respect to the ablating laser beam. The present inventionrepresents a general method for ultrashort pulsed laser surface millingof a surface that may move or change during the ablation process.

While my above description contains many specificities, these should notbe construed as limitations on the scope of the invention, but rather asan exemplification of preferred embodiments thereof. For example, curvedor flat applanation optics commonly used in femtosecond laser keratomesmay be combined with the invention to perform incisional maneuvers.

Accordingly, the scope of the invention should be determined not by theembodiments illustrated, but by the appended claims and their legalequivalents.

I claim:
 1. A method for producing high optical contrast fiduciary marksin biologic tissue comprising the steps of: a. focusing short orultrashort laser pulses on a cornea; b. scanning in a predeterminedincisional pattern; and c. marking one or more incisions with theapplication of an optical contrast agent, wherein the fiduciary marksare advantageous for optical tracking and motion correction of targetedtissue.
 2. The method of claim 1, further comprising the step ofverifying proper fixation of a laser on a patient's eye prior toinitiating the scanning.
 3. The method of claim 2, wherein an opticalmeans is used to verify the proper fixation of the laser.
 4. The methodof claim 2, wherein verifying proper fixation of the laser comprisesvisualizing the patient's eye and the fiduciary marks and using auser-interface to determine an appropriate offset value.
 5. The methodof claim 1, wherein a width and a depth of the one or more incisions isminimized to avoid interfering with visual acuity of a patient.
 6. Themethod of claim 5, wherein the width of the one or more incisions is 1to 30 microns, wherein the width of the one or more incisions isoptimally 5 to 15 microns, and wherein the depth of the one or moreincisions is 10 to 100 microns, wherein the depth of the one or moreincisions is optimally 20 to 50 microns.
 7. The method of claim 1,wherein the one or more incisions are made in a stromal bed, wherein thestromal bed is exposed by cutting and lifting a corneal flap.
 8. Themethod of claim 1, wherein the one or more incisions are made in aposterior surface of a corneal flap.
 9. The method of claim 1, whereinthe one or more incisions are made on an anterior surface of the cornea.10. The method of claim 1, wherein the contrast agent is applied byirrigating or wiping the contrast on the one or more incisions.
 11. Themethod of claim 1, further comprising the step of removing excesscontrast agent from a patient's eye, wherein the excess contrast agentis washed or dabbed away to leave a significant amount of agent in theone or more incisions.
 12. The method of claim 1, wherein the contrastagent is selected from the group consisting of biocompatible dyes,ophthalmic fluorescent dyes, biocompatible optical scattering agents,biodegradable agents, and biocompatible pigments.